Blog RSS https://www.vumc.org/lacy-lab/ en Broadening the Microbiome: Fungi in Inflammatory Bowel Diseases (IBD) https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/broadening-microbiome-fungi-inflammatory-bowel-diseases-ibd <span class="field field--name-title field--type-string field--label-hidden">Broadening the Microbiome: Fungi in Inflammatory Bowel Diseases (IBD)</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Mon, 03/07/2022 - 08:51</span> <a href="/lacy-lab/blog-post-rss/338" class="feed-icon" title="Subscribe to Broadening the Microbiome: Fungi in Inflammatory Bowel Diseases (IBD)"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Tina C.</div> <div class="field field--name-field-barista-posts-external-url field--type-link field--label-hidden field__item"><a href="https://asm.org/Articles/2021/July/Broadening-the-Microbiome-Fungi-in-Inflammatory-Bo" target="_blank">https://asm.org/Articles/2021/July/Broadening-the-Microbiome-Fungi-in-Inflammatory-Bo</a></div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="text-indent:.5in">I recently read a blog post by Christy Clutter that discusses the role of fungi in Inflammatory bowel disease (IBD). IBD is characterized by immune hyperactivation that damages the intestine of about 3 million Americans, and includes Crohn’s disease and ulcerative colitis. Although 240 genetic variations associated with increased likelihood of IBD development have been identified, epidemiological studies show that strong environmental factors such as diet, antibiotic exposure, and smoking can affect individual susceptibility. Inappropriate immune responses to the microbes existing in the intestine could result in the development of IBD; therefore, it is important to understand how these environmental factors drive disease susceptibility in the gut microbiome.</p> <p>Most microbiome research is focused on bacterial populations because they make up trillions of organisms, but bacteria are not the only microbes that inhabit the gut. Less than 1% of microbiota studies have included fungi which leaves current knowledge of microbiomes under characterized. Although most gut microbes are bacteria, fungi have been implicated in causal roles for gut microbial ecology and host immune functionality in mice (Bernardes, et al. 2020). Current sequencing tools for fungi and bacteria are similar, but there is a lack of diversity in the species identified due to sampling, and data analyses methods are biased to a small set of over-represented species. The author states that fungal reference databases used to identify sequences are "fledgling", and that bioinformatic ability to trust these taxonomic identifications is imperfect. I would argue that current databases of fungi sequencing data are suitable for trustworthy phylogenetic and taxonomic identifications. The National Center for Biotechnology Institute has a plethora of fungi sequence data that is updated daily, most notably to mycologists is the Fungal RefSeq database that includes more than 200 species (Robbertse &amp; Tatusova 2011). Most fungi identified in the clinical laboratories are yeast, and all 1,200 known species of yeast have now been sequenced by the Y1000+ Project (Shen, et al. 2018). The Y1000+ Project has sequenced the highest number of fungal species thus far, and the final version of the publicly available database will include all yeast fungal species (<a href="https://y1000plus.wei.wisc.edu/">https://y1000plus.wei.wisc.edu/</a>).  </p> <p>Scientists studying IBD have taken interest in fungi because like bacteria, they are ubiquitous in the body, and are sensitive to environmental factors such as diet. Patients with Crohn's disease have elevated circulating antifungal antibodies, and some species such as Candida albicans actively worsen inflammatory colitis in mice (Jawhara, et al. 2008). Fungi influence bacterial dynamics in the gut by acting in cooperation with host infection and biofilm production. For example, Candida tropicals can work with bacteria such as Escherichia coli and Serratia marcescens to generate a "monstrous biofilm", as well as induce the expression of fungal markers for pathogenicity (Hoarau, et al. 2016). Recent studies have shown that there is dysbiosis not only with bacterial species but also fungal species in patients with IBD. There exists inherent competition between fungi and bacteria within the gut, which means that antibiotics used to treat intestinal disease can disrupt more than just bacterial communities. Antibiotics selectively eliminate specific bacteria while leaving fungal species undisturbed, thus they can change the dysbiosis in the gut microbiome resulting in higher prominence of fungal species. Even though there is much research on the gut microbiome, little is still known about the diversity of its key microbial players. Databases such as Fungal RefSeq and Y1000+ could be a great resource in the development of specialized methods for identifying which fungal species contribute to the gut microbiome of patients with IBDs. </p> <p>References</p> <p>Bernardes E., Pettersen V.K., Gutierrez M.W., Laforest-Lapointe I., Jendzjowsky N.G., Cavin J.B., Vicentini F.A., Keenan C.M., Ramay H.R., Samara J., MacNaughton W.K., Wilson R.A., Kelly M.M., McCoy K.D., Sharkey K.A., Arrieta M.C. (2020). Intestinal fungi are causally implicated in microbiome assembly and immune development in mice. Nat Commun. 11(1):2577. doi: 10.1038/s41467-020-16431-1.</p> <p>Hoarau, G., Mukherjee, P.K., Gower-Rousseau, C., Hager, C., Chandra, J., Retuerto, M.A., Neut, C., Vermeire, S., Clemente, J., Colombel, J.F., Fujioka, H., Poulain, D., Sendid, B., Ghannoum, M.A (2016). Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn's Disease. mBio, 7(5):e01250-16. <a href="https://doi.org/10.1128/mBio.01250-16">https://doi.org/10.1128/mBio.01250-16</a></p> <p>Jawhara, S., Thuru, X., Standaert-Vitse, A., Jouault, T., Mordon, S., Sendid, B., Desreumaux, P., Poulain, D. (2008). Colonization of Mice by Candida albicans Is Promoted by Chemically Induced Colitis and Augments Inflammatory Responses through Galectin-3, The Journal of Infectious Diseases, 197(7), 972–980. <a href="https://doi.org/10.1086/528990">https://doi.org/10.1086/528990</a></p> <p>Robbertse, B., &amp; Tatusova, T. (2011). Fungal genome resources at NCBI. Mycology, 2(3), 142–160. <a href="https://doi.org/10.1080/21501203.2011.584576">https://doi.org/10.1080/21501203.2011.584576</a></p> <p>Shen, X.X., Opulente, D.A., Kominek, J., Zhou, X., Steenwyk, J.L., Buh, K.V., Haase, M.A.B., Wisecaver, J.H., Wang, M., Doering, D.T., Boudouris, J.T., Schneider, R.M., Langdon, Q.K., Ohkuma, M., Endoh, R., Takashima, M., Manabe, R.I., Cadez, N., Libkind, D., Rosa, C.A., DeVirgilio, J., Hulfachor, A.B., Groenewald, M., Kurtzman, C.P., Hittinger, C.T., Rokas, A. (2018). Tempo and mode of genome evolution in the budding yeast subphylum. Cell 175: 1533-45. <a href="https://doi.org/10.1016/j.cell.2018.10.023">https://doi.org/10.1016/j.cell.2018.10.023</a></p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/TinaC.jpg?itok=w6y5rKbt" width="506" height="576" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=5" hreflang="und">Blog Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Mon, 07 Mar 2022 14:51:30 +0000 lacydb1 338 at https://www.vumc.org/lacy-lab Evolution of a Protective Symbiont in Honey Bees by Professor Irene Newton, PhD https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/evolution-protective-symbiont-honey-bees-professor-irene <span class="field field--name-title field--type-string field--label-hidden">Evolution of a Protective Symbiont in Honey Bees by Professor Irene Newton, PhD</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Thu, 03/03/2022 - 13:01</span> <a href="/lacy-lab/blog-post-rss/336" class="feed-icon" title="Subscribe to Evolution of a Protective Symbiont in Honey Bees by Professor Irene Newton, PhD"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Monique Porter</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Speaker Background:  Dr. Irene Newton, PhD, specializes in mechanisms of symbiosis; specifically, the molecular mechanisms of host-microbe symbiotic interactions. She obtained her PhD from Harvard University and conducted postdoctoral research at Tufts University. She is currently an associate professor at Indiana University. </span></span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Seminar Summary:</span><i><span style="font-family:&quot;Times New Roman&quot;,serif"> Apis mellifera</span></i><span style="font-family:&quot;Times New Roman&quot;,serif">, the western honey bee, develop from egg to pupae within their colony. Throughout the development, they come into contact with different microbiota (<i>Gilliamella, Snodgrassella, Bombella, Lactobacillus</i>) through nectar, pollen, and interaction with other bees. These interactions can establish the gut microbiota, help protect against potential pathogens, and aid in nutrient acquisition. Using honey bees as models, Newton aimed to study how society, genetics, and behavior affect the microbial community.</span></span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">First, Newton examined the queen microbiome during and after development. She sampled both queens and workers at various time points of development to determine the microbiota and if the queens and workers microbiota were similar, indicating microbial exchange. In her findings, Newton explained that the worker and queen microbiota are distinct, and do not share microbial composition. The queens were also variable in the microbial composition and titer.</span></span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Community composition of the workers contain the “core” microbes. However, the queens had a larger composition of microbes, especially Bombella. Bombella is often referred to as the queen microbiota since it is not found commonly in the worker digestive tract. Newton attributed the differences in microbiota in queens vs. workers to physiological differences, since queens have larger ovaries and live for years, while workers typically live for 3-4 weeks. Also, queens are fed royal jelly, a specific diet that rears queen bees. Newton hypothesized that the royal jelly is pre-inoculated with <i>Bombella apis</i>, developing a distinct queen microbiota. </span></span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Next, Newton aimed to better understand the origin of <i>B. apis</i>, and its relationship with royal jelly. Through phylogenetic analysis, her team determined that <i>B. apis</i> is closely related to <i>Saccharibacter</i>, a flower-associated organism. Through sequence composition, synteny, phylogenetic methods, and functional analysis, she questioned if there were horizontally transferred regions between flower-associated <i>Saccharibacter</i> and <i>B. apis. </i>Results revealed that HGT1 is conserved across <i>B. apis</i> honeybee strains, and its function is currently unknown. HGT4 and HGT5 are also conserved and are metabolic gene regions that aid in immune defenses and the metabolism of sugars. Overall, <i>B.apis</i> acquired multiple metabolic and defense gene regions that protect the honey bee from other pathogens, and these genes contain signatures of honey bee association as they are distinct from <i>Saccharibacter</i>, a flower-associated organism. </span></span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Personal Review: I found Dr. Newton’s presentation very interesting and impactful. I broadly have experience with bumble bee microbiota, but honey bees are very different, and so is their microbiota. As Dr. Newton mentioned in her presentation, microbiome research is almost exclusive to workers and not queens. Even in bumble bee research, studies exhaustively use workers, but queen health homeostasis is much less understood. Dr. Newton was not only able to include queen microbiota samples, but additionally, relate and compare it back to workers. This study is very impactful to the field and combining the wet lab data collection and the dry lab data analysis is impressive, and it makes me excited to find out what her team is doing next. Dr. Irene Newton is a scientist I would love to connect with in the future, and I am fortunate to hear about her research through the Vanderbilt Microbiome Innovation Center.</span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Note: Seminar was presented on Wednesday, October 14<sup>th</sup>, 2020, and was viewed on </span><br /> <a href="https://www.youtube.com/channel/UC5yvWj6x4STvXf8lJO7KjIQ"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:blue">Vanderbilt Microbiome Innovation Center</span></span></a><span style="font-family:&quot;Times New Roman&quot;,serif"> channel on YouTube. </span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif"><a href="https://www.youtube.com/watch?v=nBDIjsgSzZ4&amp;t=601s">https://www.youtube.com/watch?v=nBDIjsgSzZ4&amp;t=601s</a></span></span></span></p> <p> </p> <p> </p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/monique.jpg?itok=XvugBGAj" width="266" height="576" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=11" hreflang="und">Seminar Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Thu, 03 Mar 2022 19:01:58 +0000 lacydb1 336 at https://www.vumc.org/lacy-lab Can Gut Microbes Cause Cancer? https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/can-gut-microbes-cause-cancer <span class="field field--name-title field--type-string field--label-hidden">Can Gut Microbes Cause Cancer?</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Wed, 03/02/2022 - 08:06</span> <a href="/lacy-lab/blog-post-rss/335" class="feed-icon" title="Subscribe to Can Gut Microbes Cause Cancer?"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Amelia Cephas</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">            The Western-style diet is chock full of high fat, processed and refined foods that often cause systemic damage to the human body. One particular effect that high fat foods have on the body involves the microbes in the gastrointestinal tract. Many studies have shown the association between the colonization of a subset of microbes in the gut and colorectal and gastric cancer onset. The question of interest is: can what we eat really lead to the onset of gastrointestinal cancer?</span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">            Interestingly, diet directly affects the types of bacteria that typically colonize the gut. Though both extrinsic (e.g., diet, medications) and intrinsic factors (genetics, metabolic regulation, etc.) determine the bacterial composition within the gut, the former has the most predominant effect (1). For instance, fiber-rich foods such as nuts, legumes, grains, vegetables and fruit are associated with the growth of <i>Bifidobacterium,</i> <i>Lactobacillus</i> and lactic acid bacteria. These foods, also known as prebiotics, lead to the production of butyrate, acetate, propionate and short chain fatty acids by obligate anaerobes such as those in the <i>Firmicutes</i> and <i>Bacteroidetes</i> phyla (1). On the other hand, the consumption of high fat foods leads to the increase in facultative anaerobes in the gut such as <i>Enterobacteriaceae</i>, which are abundant in the feces of individuals on high fat diets (2). Thus, a healthy intestinal environment has a hypoxic colonic surface, generally, while an unhealthy gut contains more terminal electron receptors such as oxygen and nitrate in the colonic epithelia, which facultative anaerobes use to survive in the gut (2). Ultimately, it’s safe to say the cliché: “you are what you eat”, as the microbes in your gut will tell a great deal about what you generally consume.</span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">So, what is the link between these microbes and cancer? The answer is not so simple, but a recent <i>Science</i> paper might hold some insight. In this paper, researchers sought to determine how diet-induced changes in intestinal physiology alter the metabolic capacity of the microbiota. Using a high-fat and low-fat feeding model, they showed that high-fat diet fed mice had gut epithelial metaplasia, increased abundance of <a href="#_ftn1" name="_ftnref1" title="" id="_ftnref1"><span class="MsoFootnoteReference" style="vertical-align:super"><span class="MsoFootnoteReference" style="vertical-align:super"><span style="font-size:12.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">[1]</span></span></span></span></a>, mucosal inflammation, reduced mitochondrial activity, reduced hypoxia, and that a prolonged high-fat diet escalates <i>Escherichia </i>c<i>oli</i> choline metabolism (3). Interestingly, several species of <i>E</i>.<i>coli (</i>e.g<i> pks+)</i> and other Enterobacteria are detected more frequently in patients with colorectal cancer (CRC) compared to healthy individuals. These genotoxic metabolites, which damage DNA and are found to induce mutation in genes (e.g Adenomatous polyposis coli-APC) (2, 4). Mutations that disrupt APC signaling pathways are found in 80% of CRC patients.  The fact that approximately 65% of CRC cases are sporadic, and environmental factors such as diet are likely to play a major role in its onset should be a warning to individuals who tend to ignore their nutritionists and doctors!</span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><b><u>References</u></b>:</span></span></p> <ol> <li style="margin-left:8px"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Leeming ER, Johnson AJ, Spector TD, Le Roy CI. Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration. Nutrients. 2019 Nov 22;11(12):2862. doi: 10.3390/nu11122862  </span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Foegeding NJ, Jones ZS, Byndloss MX. Western lifestyle as a driver of dysbiosis in colorectal cancer. Dis Model Mech. 2021 May 1;14(5): doi: 10.1242/dmm.049051.</span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"> <span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Yoo W, Zieba JK, Foegeding NJ, Torres TP, Shelton CD, Shealy NG, Byndloss AJ, Cevallos SA, Gertz E, Tiffany CR, Thomas JD, Litvak Y, Nguyen H, Olsan EE, Bennett BJ, Rathmell JC, Major AS, Bäumler AJ, Byndloss MX. High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine <i>N</i>-oxide. Science. 2021 Aug 13;373(6556):813-818. doi: 10.1126/science.aba3683. </span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#212121">Dougherty MW, Jobin C. Shining a Light on Colibactin Biology. Toxins (Basel). 2021 May 12;13(5):346. doi: 10.3390/toxins13050346. </span></span></span></span></li> </ol> <div>  <hr align="left" size="1" width="33%" /> <div id="ftn1"> <p class="MsoFootnoteText"><span style="font-size:10pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><a href="#_ftnref1" name="_ftn1" title="" id="_ftn1"><span class="MsoFootnoteReference" style="vertical-align:super"><span class="MsoFootnoteReference" style="vertical-align:super"><span style="font-size:10.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">[1]</span></span></span></span></a> <span style="font-size:9.0pt">High fat foods are rich in choline, which is catabolized by gut microbes</span></span></span></p> </div> </div> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/amelia.jpg?itok=i1Dlz56N" width="512" height="511" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Wed, 02 Mar 2022 14:06:36 +0000 lacydb1 335 at https://www.vumc.org/lacy-lab Journey into a mosquito https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/journey-mosquito <span class="field field--name-title field--type-string field--label-hidden">Journey into a mosquito</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Tue, 03/01/2022 - 12:35</span> <a href="/lacy-lab/blog-post-rss/334" class="feed-icon" title="Subscribe to Journey into a mosquito"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Chiamaka D. Okoye</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="margin-left:24px; text-indent:.25in"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">Mosquitoes beat humans as the world’s deadliest animals.<sup>1</sup> This is not because they directly kill people, but instead they are really good at being vectors, which are organisms that act as vehicles for pathogens to transfer between hosts. Mosquitoes are notorious for transmitting viruses like yellow fever and dengue, bacteria that cause Lyme disease and typhus, protozoans that cause malaria, and metazoans that cause lymphatic filariasis, to name a few. These pathogens are often acquired by the mosquito via horizontal transmission through an intermediate host. The ability of the mosquito to acquire and transmit pathogens to susceptible hosts, or its ‘vector competence,’ is influenced by numerous internal factors like its preference for host, time taken for the pathogen to develop within the host, and the microbiome, as well as external factors like temperature and predator density.<sup>2</sup></span></span></span></p> <p style="margin-left:24px; text-indent:.25in"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">Malaria is one of the most devastating diseases transmitted by mosquitoes. This disease is endemic in over 100 countries with a tropical climate, infecting about 229 million people as of 2020 and causing about 409,000 deaths annually, mostly in children.<sup>3</sup> Symptoms of the disease may include fever, chills, vomiting, exhaustion, anemia, and organ failure. The <i>Plasmodium </i>parasites are the causative agents of malaria in humans. <i>Plasmodium</i> falls under the Apicomplexa phylum which consist of parasitic, unicellular eukaryotes that use an apical complex to invade a host cell during part of their lifecycle. For <i>Plasmodium,</i> its lifecycle involves two hosts – mosquitoes and humans. In the mosquito, the parasite undergoes sexual reproduction; the macro and micro gametocytes ingested during a blood meal encounter each other in the mosquito’s gut to form oocytes, which progress to form several thousand copies of sporozoites. When a mosquito encounters a human host, it delivers the sporozoites along with its saliva. The sporozoites migrate to the liver where they are amplified and progress to form merozoites that can infect red blood cells. The merozoites replicate to produce about 30 more copies each, before lysing the red blood cells, which causes anemia, and going on to replenish gametocytes that get ingested by mosquitoes to propagate the cycle.<sup>2</sup></span></span></span></p> <p style="margin-left:24px; text-indent:.25in"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">Considering that we would be saving many lives each year by eradicating mosquitoes, why don’t we just kill them off? The truth is that not all mosquitoes are bad; there are about 3,500 species of which only the blood-sucking females of 100 species are vectors for parasites. Most mosquitoes feed off plant-based sources and serve as food for birds, fish, and other animals in the ecosystem.<sup>4</sup> Hence, killing them off would most likely come with negative environmental consequences. Alternative approaches have turned to making mosquitoes resistant to the parasites they transmit.<sup>4</sup> For example, the Australian-based World Mosquito Program breeds mosquitoes that carry <i>Wolbachia </i>bacteria to prevent the spread of viruses like dengue, Zika, yellow fever and chikungunya.<sup>5</sup> <i>Wolbachia </i>is proposed to function by activating host immunity in mosquitoes or by competing for cellular resources with the RNA viruses they transmit.<sup>6</sup> Other groups are looking to genetically modify mosquitoes to prevent parasitic transmission.<sup>7</sup><span class="msoIns" style="text-decoration:underline"><span style="color:teal"><ins cite="mailto:Jensen,%20Jaime%20Lea" datetime="2022-02-16T13:42"> </ins></span></span></span></span></span></p> <p style="margin-left:24px; text-indent:.25in"> </p> <p style="margin-left:24px; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><b>References</b></span></span></span></p> <p class="EndNoteBibliography" style="margin-left:29px; text-indent:-.3in"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">1.     Gates, B. The deadliest animal in the world. <a href="https://www.gatesnotes.com/health/most-lethal-animal-mosquito-week" style="color:#0563c1; text-decoration:underline">https://www.gatesnotes.com/health/most-lethal-animal-mosquito-week</a>.</span></span></p> <p class="EndNoteBibliography" style="margin-left:29px; text-indent:-.3in"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">2.     Hillyer, J., IGP 8002 - Adventure guide to the microbial world: Journey into a mosquito. 2022.</span></span></p> <p class="EndNoteBibliography" style="margin-left:29px; text-indent:-.3in"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">3.     <i>World malaria report 2020</i>; Global Malaria Programme, 30 November, 2020.</span></span></p> <p class="EndNoteBibliography" style="margin-left:29px; text-indent:-.3in"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">4.     Bates, C., Would it be wrong to eradicate mosquitoes? 28 January, 2016.</span></span></p> <p class="EndNoteBibliography" style="margin-left:29px; text-indent:-.3in"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">5.     World Mosquito Program. <a href="https://www.worldmosquitoprogram.org/en/work/about-us" style="color:#0563c1; text-decoration:underline">https://www.worldmosquitoprogram.org/en/work/about-us</a>.</span></span></p> <p class="EndNoteBibliography" style="margin-left:29px; text-indent:-.3in"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">6.     Pimentel, A. C.;  Cesar, C. S.;  Martins, M.; Cogni, R., The Antiviral Effects of the Symbiont Bacteria Wolbachia in Insects. <i>Frontiers in Immunology </i><b>2021,</b> <i>11</i>.</span></span></p> <p class="EndNoteBibliography" style="margin-left:29px; text-indent:-.3in; margin-bottom:11px"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">7.     Pike, A.;  Dong, Y.;  Dizaji, N. B.;  Gacita, A.;  Mongodin, E. F.; Dimopoulos, G., Changes in the microbiota cause genetically modified Anopheles to spread in a population. <i>Science </i><b>2017,</b> <i>357</i> (6358), 1396-1399.</span></span></p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Okoye.jpg?itok=iB7-VBlW" width="576" height="413" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Tue, 01 Mar 2022 18:35:03 +0000 lacydb1 334 at https://www.vumc.org/lacy-lab A Tick's Meal https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/ticks-meal <span class="field field--name-title field--type-string field--label-hidden">A Tick&#039;s Meal</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Thu, 02/24/2022 - 14:21</span> <a href="/lacy-lab/blog-post-rss/333" class="feed-icon" title="Subscribe to A Tick&#039;s Meal"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Kacie Traina</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">            On episode 258 of the podcast “This Week in Microbiology”, Vincent Racaniello, Elio Schaechter, Michele Swanson, and Michael Schmidt discussed two main topics focused on anti-genetic variation within dengue virus serotypes and how a novel mRNA vaccine could induce antibodies against tick proteins to prevent transmission of Lyme disease. The first portion of the episode discussed dengue, which is a single-stranded, enveloped RNA virus that causes over 50 million known cases per year. There are four different serotypes, or distinct variations, of dengue that lead to infection in humans. With the rate of infection and different serotypes, understanding more about the immunology of dengue and especially the variation between these serotypes is very important. </span></span></span></span></p> <p style="text-indent:.25in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">      One of the main topics discussed was whether antigenic variation made the dengue virus more fit. To assess if there was a fitness advantage with the dengue serotypes, studies looked at the pattern of serotypes from over 8,000 infections during outbreaks in Southeast Asia from 1970 to 2015. It was concluded that antigenic fitness is a major driver of dengue infection population genetics from year to year. Recovery from dengue infection is believed to provide lifelong immunity against that specific serotype. However, cross-immunity, the protection against a given pathogen resulting from immunity acquired from past exposure to a related pathogen or its antigens, of one dengue serotype to the other serotypes after recovery is only partial and temporary. Subsequent infections by other serotypes increase the risk of developing more severe dengue. Research showed that protection against a dengue serotype dropped 63% each year for the first two years following a dengue infection. I think understanding more about the serotypes and population genetics as performed in this study could be greatly beneficial in further development of treatments or a vaccine against dengue. Similar to the mutating variants of SARS-CoV-2 and the various influenza strains we encounter each year, understanding and being able to predict prominent serotypes of dengue could help reduce the rate of infections. </span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">            The second story in this episode of “This Week in Microbiology” focused on the creation of an mRNA vaccine that induces antibodies against tick proteins and prevents the transmission of Lyme disease, as described in a recent publication (</span></span><span style="font-family:&quot;Times New Roman&quot;,serif">Sajid, A. et al<span style="color:black">). Black-legged ticks transmit the bacteria <i>Borrelia burgdorferi</i>, which causes Lyme disease. The authors of the paper aimed to develop a new tool to prevent the spread of Lyme disease: a vaccine that stops ticks from feeding properly once they latch onto a host’s skin, which stops them from transmitting <i>B. burgdorferi</i>. Guinea pigs can develop a natural resistance to tick bites after being repeatedly bitten. At the tick bite sites, guinea pigs develop an inflamed, red welt and the immune reaction interferes with the tick’s ability to continue drinking the blood of its host. Evidence suggests that humans can also build up similar resistance to ticks. Building off of this idea of tick immunity, researchers sought to develop a vaccine to help humans become better protected from tick-borne pathogens like <i>B. burgdorferi.</i> </span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">              When a tick feeds, it takes time for the bacteria to be transmitted so the tick must remain attached for 36-48 hours. The tick’s spit helps it avoid discovery during feeding because the saliva contains proteins that suppress the host’s immune response, which reduces the amount of pain and inflammation triggered by the bite. The authors developed an mRNA vaccine using a complex blend of 19 different tick salivary proteins to help provide host protection specifically against those proteins. The goal of the vaccine was to give the host the chance to see these antigens first, before being bitten, in order to develop immunity. To test the vaccine, guinea pigs were immunized and their blood was tested for antibodies against the salivary proteins. The authors found antibodies against 10 out of 19 of the proteins two weeks after vaccination, showing an antibody-specific immune response. To further test the vaccine, the researchers placed black-legged ticks on the guinea pigs to assess if the bites would trigger an immune response. The vaccinated guinea pigs developed substantial redness around the tick bites in comparison to the unvaccinated guinea pigs which showed minimal redness. After 48 hours, some of the ticks began to detach from the vaccinated guinea pigs and 80% had completely detached after 96 hours. In a final experiment to test the vaccines’ ability to reduce the risk of Lyme disease, <i>B. burgdorferi</i>-positive ticks were placed on guinea pigs. In the unvaccinated guinea pig group, 6 out of 13 tested positive for <i>B. burgdorferi </i>but all of the vaccinated guinea pigs tested negative. This showed that not only could the vaccine mount an immune response against tick bites, it could also prevent the spread of Lyme disease in guinea pigs.</span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">            In my opinion, the study of dengue serotypes and tick mRNA vaccines present two crucially important areas in global host-pathogen interactions and infections. Understanding the patterns and differences between the dengue serotypes provides new insight into predicted outbreaks and potential treatments for those infected. The novel tick mRNA vaccine shows great potential at providing immunity to a variety of tick-borne pathogens that cause disease in humans. Future directions can focus on targeting the other 9 salivary proteins where immunity wasn’t detected in guinea pigs and then preparing the mRNA vaccine for humans. </span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><u><span style="font-family:&quot;Times New Roman&quot;,serif">References:</span></u></span></span></p> <ul> <li style="text-align:justify; margin-left:8px"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Sajid, A. et al. mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. <i>Sci.Transl Med.</i> <a href="https://doi.org/10.1126/scitranslmed.abj9827&amp;nbsp">https://doi.org/10.1126/scitranslmed.abj9827&amp;nbsp</a>;(2021)</span></span></span></li> </ul> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Kacie.jpg?itok=8e1Eho8W" width="148" height="176" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=7" hreflang="und">TWiM</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Thu, 24 Feb 2022 20:21:16 +0000 lacydb1 333 at https://www.vumc.org/lacy-lab Microbial Origins of Body Odor https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/microbial-origins-body-odor <span class="field field--name-title field--type-string field--label-hidden">Microbial Origins of Body Odor</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Wed, 02/23/2022 - 08:20</span> <a href="/lacy-lab/blog-post-rss/332" class="feed-icon" title="Subscribe to Microbial Origins of Body Odor"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Elizabeth Semler</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">A rose in full bloom, a fresh pot of brewed coffee, and a raging bonfire are only three of the millions of scents that the human olfactory system can detect. While humans are able to distinguish between many different types of odors, not all are as pleasant as a rose in full bloom. Take for instance, bromhidrosis (i.e., body odor) – a common yet often unpleasant phenomenon <span style="background:white">in post-pubertal individuals. Human body odor is caused by many factors including sex, diet, health, and disease; however, the main contributor to body odor is due to the activity of bacteria on sweat glands<sup>1-2</sup>. </span></span></span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Humans have three types of sweat glands: eccrine, apocrine and apoeccrine sweat glands, as well as sebaceous glands which influence the composition of sweat<sup>1-3</sup>. Although eccrine sweat glands are the most ubiquitous and are responsible for the largest volume of sweat excretion, bromhidrosis is due to the interaction of apocrine sweat glands with various microorganisms<sup>2-4</sup>. Unlike eccrine glands, apocrine sweat glands are restricted mainly to the axillary region, ear canals, the wings of nostrils and the perineal region. Apocrine glands produce an odorless fluid composed of proteins, lipids, fatty acids, branched-chain amino acids, vitamins, and steroids (i.e., sweat) that is discharged into the canals of hair follicles<sup>2-4</sup>. It's not until the apocrine sweat is metabolized by axillary microorganisms such as <i><span style="background:white">Micrococcaceae, Propionibacteria</span></i><span style="background:white">, <i>Staphylococcus </i>and nondiptheiroid <i>Corynebacterium</i> species </span>does it develop its characteristic odor<sup>4-6</sup>. </span></span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">A major odorant responsible for the onion-like malodor is <span style="background:white">generated mainly by <i>Staphylococcus hominis,</i></span> and is composed of <span style="background:white">volatile sulfur compounds such as 3-Methyl-3-sulfanylhexanol<sup>3-6</sup><i>. </i>These volatile sulfur compounds are secreted by apocrine glands as glycine-cysteine conjugates and are enzymatically cleaved by bacterial dipeptidases and C-S lyases which release odoriferous mercaptoalcohols<sup>3-6</sup>. Other malodors include the volatile fatty acid 3-methyl-2-hexenoic acid (3M2H), which has a goat-like odor, and 3-methyl-3-hydroxy-hexanoic acid, which has a cumin like odor<sup>3-6</sup>. Studies indicate that 3M2H is released from the skin surface after interacting with <i>Corynebacterium</i> <i>striatum</i> and <i>Corynebacterium</i> <i>bovis</i><sup>3-6</sup>. Another common malodor that is characterized by its vinegar-like smell is caused by <i>Propionibacterium </i>metabolizing glycerol and lactic acid, leading to the production of acetic and propionic acid<sup>3-6</sup>. </span></span></span></span></span></p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">The composition of the skin microbiota is diverse and can be functionally distinct between individuals. The skin microbiome and the volatile odorants produced are also dynamic and have been shown to shift in certain environments. Additionally, gastrointestinal ailments, various metabolic disorders, or even malaria can cause a change in the skin microbiome and odorants produced<sup>3-6</sup>. It is therefore important to characterize the composition of the skin microbiome and the production of axillary odorants in health and disease, as it may lead to the development of novel diagnostic tools and therapeutic treatments. </span></span></span></span></p> <p style="text-align:justify"> </p> <p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><b><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">References: </span></span></b></span></span></p> <ol> <li style="text-align:justify; margin-left:8px"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Kurosumi, K., Shibasaki, S., &amp; Ito, T. (1984). Cytology of the Secretion in Mammalian Sweat Glands. International Review of Cytology, 253–329. doi:10.1016/s0074-7696(08)62445-6 </span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Wilke K, Martin A, Terstegen L, Biel SS. A short history of sweat gland biology. Int J Cosmet Sci. 2007 Jun;29(3):169-79. doi: 10.1111/j.1467-2494.2007.00387.x. </span></span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Fredrich E, Barzantny H, Brune I, Tauch A. Daily battle against body odor: towards the activity of the axillary microbiota. Trends Microbiol. 2013 Jun;21(6):305-12. doi: 10.1016/j.tim.2013.03.002. </span></span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="background:white"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Mogilnicka I, Bogucki P, Ufnal M. Microbiota and Malodor-Etiology and Management. <i>Int J Mol Sci</i>. 2020;21(8):2886. doi:10.3390/ijms21082886</span></span></span></span></span></li> <li class="c-bibliographic-informationcitation" style="margin-bottom:8px; margin-left:8px"><span style="font-size:12pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Arial&quot;,sans-serif"><span style="color:black">Byrd, A., Belkaid, Y. &amp; Segre, J. The human skin microbiome. <i>Nat Rev Microbiol</i> <b>16, </b>143–155 (2018). <a href="https://doi.org/10.1038/nrmicro.2017.157">https://doi.org/10.1038/nrmicro.2017.157</a></span></span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:&quot;Arial&quot;,sans-serif">“Microbial Origins of Body Odor.” <i>ASM.org</i>,<a href="https://asm.org/Articles/2021/December/">https://asm.org/Articles/2021/December/</a> Microbial-Origins-of-Body-Odor. </span></span></span></li> </ol> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Semler.jpg?itok=0cDi7x2-" width="330" height="375" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Wed, 23 Feb 2022 14:20:31 +0000 lacydb1 332 at https://www.vumc.org/lacy-lab Antibiotics and Antibiotic Resistance: from Past to Present https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/antibiotics-and-antibiotic-resistance-past-present <span class="field field--name-title field--type-string field--label-hidden">Antibiotics and Antibiotic Resistance: from Past to Present</span> <div class="field field--name-field-barista-posts-category field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/lacy-lab/adventure-travel-guide-microbial-world?cat=20" hreflang="und">Class</a></div> </div> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Tue, 02/22/2022 - 08:11</span> <a href="/lacy-lab/blog-post-rss/330" class="feed-icon" title="Subscribe to Antibiotics and Antibiotic Resistance: from Past to Present"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Emily Green </div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:11.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">Imagine a world where infections that are currently viewed as minor were deadly, where your parent died from </span></span><span style="font-size:11.0pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#202124">a burn that became infected with </span></span></span></span><i><span style="font-size:11.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#202124">Staphylococcus aureus</span></span></span></i><span style="font-size:11.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#202124">, or your friend lay suffering beside you on the battlefield with sepsis as you fought for the freedom of millions of wrongfully mistreated people. This world </span></span></span><span style="font-size:11.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">is not so far away or so distant in the past . While some parts of the world sadly still struggle with this, billions of people across the globe benefit annually from antibiotic treatment of formerly deadly, pathogenic infections. As Dr. Jim Cassat details in the lecture “In Case of Emergency: Bring Antibiotics!” the discovery of antibiotics is attributed to the research of many great scientists, a few accidents, and remains a current concern in the field of modern biomedical science. </span></span></span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:11.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">The birth of clinical antibiotics is largely attributed to Sir Alexander Fleming who discovered penicillin after neglecting plates in the lab during the summer of 1928. Upon returning to the lab in the fall, he discovered a mold on the agar plates he had used months prior and began investigating the organism. Following his studies into the mold <i>Penicillium notatum</i>, Fleming published his findings a year later. While Fleming’s discovery would go on to spur a radical change in clinical microbiology, he was not the first to describe antibiotics, nor the reason for the change in production scaling that would lead to penicillin’s clinical relevance, as stressed by Dr. Cassat.</span></span></span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:11.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"> <span style="color:#2e2e2e">By 1945, penicillin ushered in the “Golden Age of Antibiotics” thanks to three English scientists- Howard Florey, Norman Heatley, and Ernst Chain, who worked to purify and amplify production of penicillin, thus allowing it to be produced in clinically relevant quantities for use during World War II (1). Fleming, Florey, and Chain were awarded a Nobel Prize in 1945, seventeen years after penicillin was first discovered. In his Nobel lecture, Fleming recognized and warned of the danger of widespread antibiotic use: </span> </span></span></span></span></p> <p> </p> <p style="margin-left:48px"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:11.0pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#3a343a">“It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body. The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.” (2). </span></span></span></span></span></span></p> <p> </p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:11.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">Fleming’s warning may have been issued the better part of a century ago, but the very words he spoke resonate the urgency of current clinical antibiotic resistance. In 2019, some U.S. states exceeded 920 antibiotic courses prescribed per 1,000 patients in clinics alone (3). Other countries such as India have unregulated antibiotics available without prescription, and agriculture across the globe has leveraged antibiotics to produce more food per acre/head. Together, the world faces an ever-increasing health threat. The CDC reports that as of 2021, 2.8 million antibiotic resistant infections occur annually in the U.S. (4).  Antibiotic use must be decreased and appropriated in an effort to alleviate selective pressures on bacterial populations and decrease the evolution of antibiotic resistance. This is an ever-growing issue considering that pharmaceutical companies are moving away from antibiotic production due to hospitals reserving new compounds for the most dire of cases, according to Dr. Cassat. In combination with a decrease in antibiotic discovery and production, the world faces a clinical crisis.  If we continue to ignore Fleming’s warning, will we force ourselves to return to a near pre-antibiotic world? </span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:11.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">References: </span></span></span></span></span></p> <ol> <li style="margin-left:8px"><span style="font-size:12pt"><span style="line-height:150%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:11.0pt"><span style="background:white"><span style="line-height:150%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Quinn R. (2013). Rethinking antibiotic research and development: World War II and the penicillin collaborative. </span></span></span></span></span><i><span style="font-size:11.0pt"><span style="line-height:150%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">American journal of public health</span></span></span></span></i><span style="font-size:11.0pt"><span style="background:white"><span style="line-height:150%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">, </span></span></span></span></span><i><span style="font-size:11.0pt"><span style="line-height:150%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">103</span></span></span></span></i><span style="font-size:11.0pt"><span style="background:white"><span style="line-height:150%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">(3), 426–434. <a href="https://doi.org/10.2105/AJPH.2012.300693">https://doi.org/10.2105/AJPH.2012.300693</a></span></span></span></span></span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="line-height:150%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:11.0pt"><span style="line-height:150%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Sir Alexander Fleming. (1945). Nobel Lecture. NobelPrize.org. Nobel Prize Outreach AB 2022. </span></span></span></span><a href="https://www.nobelprize.org/prizes/medicine/1945/fleming/lecture" style="color:#0563c1; text-decoration:underline"><span style="font-size:11.0pt"><span style="line-height:150%"><span style="font-family:&quot;Times New Roman&quot;,serif">https://www.nobelprize.org/prizes/medicine/1945/fleming/lecture</span></span></span></a></span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="line-height:150%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:11.0pt"><span style="line-height:150%"><span style="color:black">Centers for Disease Control and Prevention. (2021, November 1).</span></span></span> <i><span style="font-size:11.0pt"><span style="line-height:150%"><span style="color:black">Current report</span></span></span></i><span style="font-size:11.0pt"><span style="line-height:150%"><span style="color:black">. Centers for Disease Control and Prevention. Retrieved February2022, from </span></span></span><a href="https://www.cdc.gov/antibiotic-use/stewardship-report/current.html" style="color:#0563c1; text-decoration:underline"><span style="font-size:11.0pt"><span style="line-height:150%">https://www.cdc.gov/antibiotic-use/stewardship-report/current.html</span></span></a>         </span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="line-height:150%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:11.0pt"><span style="line-height:150%"><span style="color:black">Centers for Disease Control and Prevention. (2021, November 23).</span></span></span> <i><span style="font-size:11.0pt"><span style="line-height:150%"><span style="color:black">Tracking antibiotic resistance</span></span></span></i><span style="font-size:11.0pt"><span style="line-height:150%"><span style="color:black">. Centers for Disease Control and Prevention. Retrieved February 2022, from <a href="https://www.cdc.gov/drugresistance/tracking.html">https://www.cdc.gov/drugresistance/tracking.html</a></span></span></span> </span></span></span></li> </ol> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/EmilyGreen_0.jpg?itok=cVAmB-X9" width="409" height="543" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Tue, 22 Feb 2022 14:11:47 +0000 lacydb1 330 at https://www.vumc.org/lacy-lab Viruses can do that too? https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/viruses-can-do-too <span class="field field--name-title field--type-string field--label-hidden">Viruses can do that too?</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Tue, 02/09/2021 - 19:58</span> <a href="/lacy-lab/blog-post-rss/313" class="feed-icon" title="Subscribe to Viruses can do that too?"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Microbial_wanderlust</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p class="MsoNormal" style="text-indent:.5in">Bacteriophages, or phages, are a type of virus that specifically target bacteria for resources and reproduction<sup>1</sup>. The diversity of phages in size, functional capability, and genetic information is exponentially increasing as more are discovered and characterized. In general, phage infect a specific species of bacteria. Almost all phages have similar structures, consisting of a capsid “head” that stores genetic information and a “tail” that is used to interact with a host. Like other viruses, phages do not have a nucleus. However, it was discovered by Vorrapon Chaikeeratisak et al. in 2017 that a set of phages that specifically infect Pseudomonas species were observed with a proteinaceous, nucleus-like compartment, or “shell”, that surrounded the phage DNA2. An example of this can be seen in Figure 4A from the paper, where they used cryo-electron tomography to show an infected cell that contained phage with the shell, represented by the phage that are darker in color.<p></p></p> <p class="MsoNormal" style="text-indent:.5in">This preliminary finding influenced the work of Senén Mendoza from the Bondy-Denomy group, who normally study CRISPR-Cas biology and function. In 2020, Mendoza and others published a paper entitled “A bacteriophage nucleus-like compartment shields DNA from CRISPR nucleases”, where they find that the previously studied “shell” can actually protect phage DNA from degradation by host CRISPR machinery<sup>3</sup>. In this study, they found that DNA the large phage ΦKZ, which exclusively infects <i>Pseudomonas aeruginosa </i>and was part of the earlier group of phages studied by Chaikeeratisak, was unaffected when the phage was challenged with an array of CRISPR enzymes. Some phages that infect <i>P. aeruginosa</i> have been previously shown to block CRISPR enzymes through the production of inhibitory proteins. However, the authors performed a genome-wide search and discovered that ΦKZ did not encode for any of these proteins. Through the use of<span class="name"> fluorescence microscopy, they were able to show that different CRISPR-Cas enzymes are unable to breach the “shell”, as shown here in Figure 2b from the paper. Here, the first column shows CRISPR enzymes labeled with mCherry and the second column shows phage DNA stained with DAPI. They also explain that, when removed from the “shell”, </span>ΦKZ<span class="name"> phage DNA is able to be cleaved by CRISPR enzymes, indicating that the lack of degradation is not due to an intrinsic feature of the DNA. Finally, the authors created a fusion protein of different CRISPR enzymes to a host protein involved in DNA replication that had been known to bypass the “shell”, though the specific mechanism by which this is achieved is unknown. This resulted in cleavage of </span>ΦKZ<span class="name"> DNA, again indicating that the nucleus-like compartment is what confers resistance to CRISPR enzymes.<p></p></span></p> <p class="MsoNormal"><span class="name"><span style="mso-tab-count:1">            </span>The authors conclude that this discovery speaks to the larger trend of growing phage diversity and highlights a unique and intriguing point of evolution in the viral realm. They propose that this shell could be observed in other, large phages that are not specific to <i>Pseudomonas sp</i>. One area in which the authors plan to continue researching is understanding how the “shell” selectively permits which enzymes are able to reach the phage DNA. This paper represents one of a growing number of reports that highlight unique features of viruses that defy expectations.</span><p></p></p> <p class="MsoNormal"><p><strong>References</strong></p></p> <p class="MsoListParagraphCxSpFirst" style="text-indent:-.25in;line-height:normal;&#10;mso-list:l0 level1 lfo1"><!--[if !supportLists]--><span style="mso-bidi-font-size:&#10;12.0pt;mso-fareast-font-family:&quot;Times New Roman&quot;"><span style="mso-list:Ignore">1.<span style="font:7.0pt &quot;Times New Roman&quot;">     </span></span></span><!--[endif]--><span style="mso-bidi-font-size:12.0pt;mso-fareast-font-family:&#10;&quot;Times New Roman&quot;">Kasman LM, Porter LD. Bacteriophages. [Updated 2020 Oct 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: <a href="https://www.ncbi.nlm.nih.gov/books/NBK493185/">https://www.ncbi.nlm.nih.gov/books/NBK493185/</a><p></p></span></p> <p class="MsoListParagraphCxSpMiddle" style="text-indent:-.25in;line-height:normal;&#10;mso-list:l0 level1 lfo1"><!--[if !supportLists]--><span style="mso-bidi-font-size:&#10;12.0pt;mso-fareast-font-family:&quot;Times New Roman&quot;"><span style="mso-list:Ignore">2.<span style="font:7.0pt &quot;Times New Roman&quot;">     </span></span></span><!--[endif]--><span style="mso-bidi-font-size:12.0pt;mso-fareast-font-family:&#10;&quot;Times New Roman&quot;">Mendoza, Senén D., et al. "A bacteriophage nucleus-like compartment shields DNA from CRISPR nucleases." <i>Nature</i> 577.7789 (2020): 244-248.<p></p></span></p> <p class="MsoListParagraphCxSpLast" style="text-indent:-.25in;line-height:normal;&#10;mso-list:l0 level1 lfo1"><!--[if !supportLists]--><span style="mso-bidi-font-size:&#10;12.0pt;mso-fareast-font-family:&quot;Times New Roman&quot;"><span style="mso-list:Ignore">3.<span style="font:7.0pt &quot;Times New Roman&quot;">     </span></span></span><!--[endif]--><span style="mso-bidi-font-size:12.0pt;mso-fareast-font-family:&#10;&quot;Times New Roman&quot;">Chaikeeratisak, Vorrapon, et al. "Assembly of a nucleus-like structure during viral replication in bacteria." <i>Science</i> 355.6321 (2017): 194-197.<p></p></span></p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Fig2b.png?itok=o5NadvO-" width="394" height="576" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=12" hreflang="und">Paper Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Wed, 10 Feb 2021 01:58:05 +0000 lacydb1 313 at https://www.vumc.org/lacy-lab Skin microbiota: Roles in barrier maintenance & repair https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/skin-microbiota-roles-barrier-maintenance-repair <span class="field field--name-title field--type-string field--label-hidden">Skin microbiota: Roles in barrier maintenance &amp; repair</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Mon, 02/08/2021 - 20:45</span> <a href="/lacy-lab/blog-post-rss/312" class="feed-icon" title="Subscribe to Skin microbiota: Roles in barrier maintenance &amp; repair"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Teresa Torres, @tsosciency</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">            In recent years, the human microbiome began to be considered one of the major organs of the human body; it is defined as the collection of all the microorganisms living in symbiosis with the body (Human Microbiome Project, NIH). The microbiome found on and within the human body comprises about one to three percent of the body’s mass and is composed of various communities including, eukaryotes, archaea, bacteria and viruses which outnumber cells in the body due to their miniscule size. As the microbe-host field continues to grow, the literature strongly implicates a link between microbial composition of the microbiome an how it may relate to numerous disease states, as well as giving a growing implication that manipulation of these microbial communities may be a potential avenue for treatment of disease.</span></span></span></span></p> <p><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">            Recently, Dr. Grice, an associate professor at the University of Pennsylvania, gave a talk for the VI4 seminar series introducing the skin microbiome as a protective barrier and a source of repair when working together with other host mechanisms of protection like innate and adaptive immune responses. The skin is able to support the growth of microorganisms due to the nutrients that are provided by the sebum released from the sebaceous gland which serves to emolliate our skin. Her research program focuses on understanding the role of the skin microbiome in skin diseases by bringing together culture-independent and culture-based approaches. The Grice lab is interested in understanding the homeostatic roles of the commensal skin microbiota and how alteration influence integrity and function of skin. To answer these questions, she has various ongoing projects in her lab; one of these projects focuses on understanding what genes during skin homeostasis are regulated specifically by the skin microbiome. A graduate student apart of the Grice lab was able to investigate this particular interest further through the use of a gnotobiotic mouse model. Comparing gene regulation of over 700 genes between specific pathogen free and germ-free mice, they were able to observe regulation of certain genes belonging to the epidermis complex. To follow up, a postdoctoral fellow, did a RNAseq study that looked into the gene ontology of the epidermis complex to better understand what pathway were affected by the skin microbiome. Their data revealed that skin and epidermal development as well as keratinocyte differentiation were heavily influenced if not regulated by the skin microbiome. It is important to note that their data was indicative of Currently they have several follow-up projects focusing on understanding what the morphological and functional implications of dysregulated gene expression when the skin microbiome is disrupted. </span></span></span></span></p> <p><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">            In 2020 the Grice Lab published an article in the journal Cell Host &amp; Microbe, where they discussed protective factors of the skin microbiome and its role in pathogen colonization resistance against bacterial microorganisms like <i>Staphylococcus aureus</i>. They focus on this specific pathogen because <i>S. aureus </i>is the leading cause for skin and soft tissue infections in the United States. The authors focused on understanding the direct and indirect protective responses provided by the skin microbiome during pathogen invasion. Their data demonstrates the direct protective factors of certain skin microorganisms like <i>Staphylococcus epidermis</i> which are able to produce antimicrobials and tolerate an immune response provide protection against <i>S. aureus </i>invasion of the skin during infection (Flowers and Grice, 2020). In a more indirect way, commensal microorganisms of the skin are able to stimulate host cells into prompting a host immune response (Flowers and Grice, 2020).</span></span></span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">I really enjoyed Dr. Grice’s seminar because it provided insight about a part of the body that has huge microbiota implications and often is not thought about. I look forward to what other fascinating results come from her lab and how it may pertain to the role of the skin microbiota in the development of skin cells. As the microbiome field continues to evolve, it is interesting to see how microorganisms may affect key roles in development and protection. </span></span></span></span></p> <p><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">References </span></span></span></span></p> <ol> <li style="margin-left:8px"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:Times">Human Microbiome Project. </span><a href="https://commonfund.nih.gov/hmp" style="color:#0563c1; text-decoration:underline"><span style="font-family:Times">https://commonfund.nih.gov/hmp</span></a><span style="font-family:Times">. August 2020. </span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="background:white"><span style="font-family:Times"><span style="color:black">Flowers L, Grice EA. </span></span></span><span style="font-family:&quot;Times New Roman&quot;,serif">“Skin microbiota: Roles in barrier maintenance &amp; repair.” VI4 Seminar. January 12, 2021. </span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="background:white"><span style="font-family:Times"><span style="color:black">Flowers L, Grice EA. The Skin Microbiota: Balancing Risk and Reward. Cell Host Microbe. 2020 Aug 12;28(2):190-200. doi: 10.1016/j.chom.2020.06.017. PMID: 32791112; PMCID: PMC7444652.</span></span></span></span></span></span></li> </ol> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Torres.png?itok=zudStLmD" width="442" height="576" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=11" hreflang="und">Seminar Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Tue, 09 Feb 2021 02:45:59 +0000 lacydb1 312 at https://www.vumc.org/lacy-lab Alcanivorax, an efficient cleaner of our oceans https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/alcanivorax-efficient-cleaner-our-oceans <span class="field field--name-title field--type-string field--label-hidden">Alcanivorax, an efficient cleaner of our oceans</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Mon, 02/08/2021 - 20:21</span> <a href="/lacy-lab/blog-post-rss/311" class="feed-icon" title="Subscribe to Alcanivorax, an efficient cleaner of our oceans"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Steven Wall</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">Our oceans are chock-full of microbes, from the clear blue waters to the darkest depths.  In fact, the reason ocean water is so clear in some areas is due to the nearly perfect utilization of nutrients in the water.  Even though many people might find the thought of bacteria disgusting, they are invaluable members of marine ecosystems.  Along with other microbial life, they are responsible for the majority of the nutrient cycling that keeps everything in homeostasis.<sup>1</sup> It is usually when humans mess things up by polluting the environment that problems occur.</span></span></span></p> <p style="margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">            It is common knowledge that hydrocarbons like plastics and crude oil are major sources of pollution in our oceans.  Plastics are such a large pollutant that there is a mass in the Pacific ocean known as the “Pacific Garbage Patch” that has been exponentially growing in size for decades, with some estimates placing it as being larger than many countries.<sup>2</sup> In a recent article from the blog <i>Small Things Considered, </i>authors Joseph A. Christie-Oleza and Vinko Zadjelovic discuss a fascinating group of bacteria that they call a “brigade of microbial cleaners”, known scientifically as obligate hydrocarbonoclastic bacteria (OHCB).<sup>3</sup> This simply means that they need to consume hydrocarbons in order to survive.   <i>Alcanivorax </i>is one such bacterial genus that belongs to this brigade, and it is the most well studied of the bunch.  Because of the niche these bacteria occupy, they exist in very low populations in ecosystems with no pollution.  It was unknown for a time how they survive for long periods of time without any sort of pollution to sustain them.  It turns out that cyanobacteria, which are the most plentiful photosynthesizers on the planet, produce alkanes that are able to sustain these OHCBs at a very low level.  </span></span></span></p> <p style="margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">            The reason that OHCBs like <i>Alcanivorax</i> can degrade alkanes is through a specific type of enzyme known as a monooxygenase.  With the help of these enzymes, OHCBs are able to oxidize long chain alkanes, such as those in crude oil, that would otherwise be unusable.  Once oxidized they can flow into the beta oxidation pathway to serve as a carbon source.  One of the potential limitations of OHCBs that the authors mention is that it is currently unclear if they can degrade extremely long chain polymers such as polyethylene that make up a large percentage of plastic waste in the oceans, however the authors seem hopeful.  In a recent paper by the same authors, they showed experimentally that <i>Alcanivorax</i> was capable of efficiently degrading synthetic aliphatic polyesters.  Like polyethylene, polyesters are extremely long chain plastic polymers, but <i>Alcanivorax</i> is able to metabolize polyesters with a special type of secreted esterase that breaks up the long chain into smaller subunits that the bacteria can utilize.<sup>4</sup>  Importantly, these aliphatic polyesters are thought of widely as being more biodegradable and eco-friendly and, as the authors say, now we know that the ocean has a way of dealing with them.  </span></span></span></p> <p style="text-indent:.5in; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">The ramifications of this research are far reaching.  <i>Alcanivorax </i>shows us that the microbial world has an untapped arsenal of powerful tools for solving problems that we are still struggling with.  We just need to put the money and effort in to finding these microbes.  It’s pretty amazing that the ocean microbiome has coevolved in this way to keep these OHCBs as a reserve emergency custodial force, ready to ramp up and do their part.</span></span></span></p> <p style="text-indent:.5in; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">References</span></span></span></p> <ol> <li style="margin-left:8px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">Sigman, D. M. &amp; Hain, M. P. (2012) The Biological Productivity of the Ocean. <i>Nature Education Knowledge</i> 3(10):21</span></span></span></li> <li style="margin-left:8px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span lang="IT" style="background:white" xml:lang="IT"><span style="color:#222222">Lebreton, L., Slat, B., Ferrari, F. <i>et al.</i> </span></span><span style="background:white"><span style="color:#222222">Evidence that the Great Pacific Garbage Patch is rapidly accumulating plastic. <i>Sci Rep</i> <b>8, </b>4666 (2018). </span></span><a href="https://doi.org/10.1038/s41598-018-22939-w" style="color:#0563c1; text-decoration:underline"><span style="background:white">https://doi.org/10.1038/s41598-018-22939-w</span></a></span></span></span></li> <li style="margin-left:8px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="background:white"><span style="color:#222222">Christie-Oleza J. A. &amp; Zadjelovic V. “Alcanivorax, an efficient cleaner of our oceans.” <i>Small Things Considered</i>, 2020, </span></span><a href="https://schaechter.asmblog.org/schaechter/2020/12/alcanivorax-an-efficient-cleaner-of-our-oceans.html" style="color:#0563c1; text-decoration:underline"><span style="background:white">https://schaechter.asmblog.org/schaechter/2020/12/alcanivorax-an-efficient-cleaner-of-our-oceans.html</span></a></span></span></span></li> <li style="margin-left:8px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:10.5pt"><span style="background:white"><span style="line-height:107%"><span style="font-family:&quot;Open Sans&quot;,sans-serif"><span style="color:#1c1d1e">Zadjelovic, V., Chhun, A., Quareshy, M., Silvano, E., Hernandez</span></span></span></span></span><span style="font-size:10.5pt"><span style="background:white"><span style="line-height:107%"><span style="font-family:&quot;Cambria Math&quot;,serif"><span style="color:#1c1d1e">‐</span></span></span></span></span><span style="font-size:10.5pt"><span style="background:white"><span style="line-height:107%"><span style="font-family:&quot;Open Sans&quot;,sans-serif"><span style="color:#1c1d1e">Fernaud, J.R., Aguilo</span></span></span></span></span><span style="font-size:10.5pt"><span style="background:white"><span style="line-height:107%"><span style="font-family:&quot;Cambria Math&quot;,serif"><span style="color:#1c1d1e">‐</span></span></span></span></span><span style="font-size:10.5pt"><span style="background:white"><span style="line-height:107%"><span style="font-family:&quot;Open Sans&quot;,sans-serif"><span style="color:#1c1d1e">Ferretjans, M.M., Bosch, R., Dorador, C., Gibson, M.I. and Christie</span></span></span></span></span><span style="font-size:10.5pt"><span style="background:white"><span style="line-height:107%"><span style="font-family:&quot;Cambria Math&quot;,serif"><span style="color:#1c1d1e">‐</span></span></span></span></span><span style="font-size:10.5pt"><span style="background:white"><span style="line-height:107%"><span style="font-family:&quot;Open Sans&quot;,sans-serif"><span style="color:#1c1d1e">Oleza, J.A. (2020), Beyond oil degradation: enzymatic potential of <i>Alcanivorax</i> to degrade natural and synthetic polyesters. Environ Microbiol, 22: 1356-1369. </span></span></span></span></span><a href="https://doi.org/10.1111/1462-2920.14947" style="color:#0563c1; text-decoration:underline"><span style="font-size:10.5pt"><span style="background:white"><span style="line-height:107%"><span style="font-family:&quot;Open Sans&quot;,sans-serif"><span style="color:#003057">https://doi.org/10.1111/1462-2920.14947</span></span></span></span></span></a></span></span></span></li> </ol> <p style="margin-bottom:11px; margin-left:48px"> </p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Steven%20Wall.png?itok=zI8Wpd5T" width="430" height="576" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=5" hreflang="und">Blog Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Tue, 09 Feb 2021 02:21:01 +0000 lacydb1 311 at https://www.vumc.org/lacy-lab The Superpowers of P. luminescens https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/superpowers-p-luminescens <span class="field field--name-title field--type-string field--label-hidden">The Superpowers of P. luminescens</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Sun, 02/07/2021 - 20:46</span> <a href="/lacy-lab/blog-post-rss/310" class="feed-icon" title="Subscribe to The Superpowers of P. luminescens"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Kateryna N.</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Arial&quot;,sans-serif">The richness of the bacterial world is truly astonishing. While it is impossible to know an exact number of bacterial species on our planet, some reports help us appreciate the scope of the bacterial diversity. According to <i>Nature Reviews, </i>“there are 100 million times as many bacteria in the oceans (13×10<sup>28</sup>) as there are stars in the known universe”.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>1</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> Other studies suggest that the Earth is home to 1 trillion (10<sup>12</sup>) microbial species.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>2</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> Considering that scientists have been able to investigate and culture only ~30,000 bacterial species</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>3</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif">, one can conclude that the fraction of the bacterial population that has been sampled so far is relatively low. It is thus remarkable how much interesting and distinct information we have learned from this relatively small representative sample of bacteria around us. <i>Photorhabdus luminescens</i> is a great example of a bacterium that has unique physiology, clinical and agricultural relevance, and potentially even a role in history.  During our introductory lecture by Dr. Hadjifrangiskou, we briefly heard about <i>P. luminescens </i>which<i> </i>caught my attention by its natural ability to luminesce. It turns out, there is much more to it than that.</span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Arial&quot;,sans-serif">The life cycle of<i> P. luminescens</i> is quite a story. The bacterium lives in symbiosis with the nematode <i>Heterorhabditis bacteriophora</i>.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>4</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> When the nematodes infect insects and enter their bloodstream, they release <i>P. luminescens</i>.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>4</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> The bacteria subsequently secrete toxins and enzymes that decompose the insect carcass.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>4</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> As a result, the symbiotic duo has food for survival and reproduction.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>4</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> Eventually, the nematodes and bacteria reassociate, emerge from the carcass, and start looking for a new insect host.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>5</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> Interestingly, according to some stories, this symbiotic relationship even had a role in the Battle of Shiloh during the American Civil War.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>6</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> It was noticed that some soldiers’ wounds began to glow in the dark, and those with glowing wounds recovered much faster.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>7</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> Although this might have been a folklore legend, an explanation for this observation, sometimes referred to as “angel’s glow”, was later provided.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>7</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> It was proposed that, in some cases, insects attracted to soldiers’ wounds were infected with the nematodes carrying <i>P. luminescens</i>.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>7</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> As a result, the luminescent bacteria got released into the soldiers' wounds causing the glowing effect.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>7</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> Nowadays, it is also known that <i>P. luminescens</i> produce many antimicrobial substances against bacterial competitors.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>5</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> Thus, <i>P. luminescens</i> could inhibit the growth of other bacteria in open wounds leading to soldiers’ recovery. The breadth of <i>P. luminescens</i>’ capabilities is fascinating to me! </span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Arial&quot;,sans-serif">Besides<i> </i>its clinical relevance,<i> P. luminescens is relevant to agriculture </i>due to its role in insect control.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>4</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> For example, insect-pathogenic nematodes carrying <i>Photorhabdus </i>species<i> </i>have been used as biopesticides in the United States and Australia.</span><span style="font-family:&quot;Arial&quot;,sans-serif"><sup>4</sup></span><span style="font-family:&quot;Arial&quot;,sans-serif"> Overall, this story made me conclude: the bacterial diversity is striking, but so is the diversity of functions within just one bacterial species, such as <i>P. luminescens</i>.</span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><b><span style="font-family:&quot;Arial&quot;,sans-serif">References</span></b><span style="font-family:&quot;Arial&quot;,sans-serif">:</span></span></span></p> <p><span style="font-size:12pt"><span style="text-autospace:none"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Arial&quot;,sans-serif">(1)  (2011) Microbiology by numbers. <i>Nat. Rev. Microbiol.</i> <i>9</i>, 628.</span></span></span></span></p> <p><span style="font-size:12pt"><span style="text-autospace:none"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Arial&quot;,sans-serif">(2) Locey, K. J., and Lennon, J. T. (2016) Scaling laws predict global microbial diversity. <i>Proc. Natl. Acad. Sci.</i> <i>113</i>, 5970 LP – 5975.</span></span></span></span></p> <p><span style="font-size:12pt"><span style="text-autospace:none"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Arial&quot;,sans-serif">(3) Dykhuizen, D. (2005) Species Numbers in Bacteria. <i>Proc. Calif. Acad. Sci.</i> <i>56</i>, 62–71.</span></span></span></span></p> <p><span style="font-size:12pt"><span style="text-autospace:none"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Arial&quot;,sans-serif">(4) Gerrard, J. G., McNevin, S., Alfredson, D., Forgan-Smith, R., and Fraser, N. (2003) Photorhabdus species: bioluminescent bacteria as emerging human pathogens? <i>Emerg. Infect. Dis.</i> <i>9</i>, 251–254.</span></span></span></span></p> <p><span style="font-size:12pt"><span style="text-autospace:none"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Arial&quot;,sans-serif">(5) Heermann, R., and Fuchs, T. M. (2008) Comparative analysis of the Photorhabdus luminescens and the Yersinia enterocolitica genomes: uncovering candidate genes involved in insect pathogenicity. <i>BMC Genomics</i> <i>9</i>, 40.</span></span></span></span></p> <p><span style="font-size:12pt"><span style="text-autospace:none"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Arial&quot;,sans-serif">(6) Youle, M. (2009) The Two Faces of Photorhabdus. <i>Small Things Consid.</i></span></span></span></span></p> <p><span style="font-size:12pt"><span style="text-autospace:none"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Arial&quot;,sans-serif">(7) Durham, S. (2001) Students May Have Answer for Faster-Healing Civil War Wounds that Glowed. <i>ARS News Inf.</i></span></span></span></span></p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Kateryna.png?itok=TWpLDNK3" width="502" height="448" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=19" hreflang="und">Lecture Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Mon, 08 Feb 2021 02:46:18 +0000 lacydb1 310 at https://www.vumc.org/lacy-lab A Microbe You May Not Know https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/microbe-you-may-not-know <span class="field field--name-title field--type-string field--label-hidden">A Microbe You May Not Know</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Sun, 02/07/2021 - 15:56</span> <a href="/lacy-lab/blog-post-rss/309" class="feed-icon" title="Subscribe to A Microbe You May Not Know"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Clostridium bonelium</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">On this episode of the podcast “This Week in Microbiology” Vincent Racaniello, Elio Schaechter, Michele Swanson, and Michael Schmidt discussed the research paper from the National Institute of Allergy and Infectious Disease (NIAID) by Myles et al. titled “Therapeutic responses to <i>Roseomonas mucosa</i> in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair” which discussed the skin microbiome and atopic dermatitis. Michael Schmidt remarked how impactful a probiotic treatment for atopic dermatitis can be for an individual’s physical health and their psyche. The clinical data were followed by a mechanistic exploration of how <i>R. mucosa</i> affects the epithelium. Contrary to the organization of most scientific papers, this paper begins with a discussion of the clinical data followed by the basic research that lead to the clinical trial. </span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Myles et al. explored the utilization of <i>R. mucosa</i> obtained from healthy individuals as a topical probiotic for individuals suffering from atopic dermatitis. Individuals with this disease contain <i>R. mucosa </i>in their skin microbiota; however, the <i>R. mucosa</i> varies from that of healthy individuals. This variation in the skin microbiota causes skin inflammation resulting in irritation and in some instances, lesions. Participants in the clinical trial were scored before and after application of cultured <i>R. mucosa</i> using existing clinical scales (SCORAD and EASI). Additionally, the authors used dose escalation in the trial which increased the concentration of <i>R. mucosa</i> over time. There was significant improvement in all patients compared to the placebo and an FDA approved drug Tacrolimus (Myles et al., 2020). This represents a great alternative to Tacrolimus and other immunosuppressive medication. Michele Swanson mentioned that the primary author involved in the clinical trial noticed a change in patient behavior. Specifically, <i>R. mucosa </i>probiotic treatment improved children’s self-confidence, which was observed by changes in behavior such as wearing short-sleeve shirts. </span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Following the results of the clinical investigation, the hosts discussed the mechanistic success of the probiotic described by the authors of the study. The microbiome of the skin was tracked over time during the clinical trial. Application of <i>R. mucosa</i> resulted in an increase in <i>Alphaproteobacteria</i> and a subsequent decrease in <i>Staphylococcaceae</i> abundance. The altered microbial populations resemble that of the skin found in healthy individuals. Cytokine levels from the skin showed anti-inflammatory properties such as IL-13 and TNF<span style="font-family:Symbol">a</span> (Myles et al., 2020). Following molecular characterization of patients’ healing tissue, the authors assessed tissue repair in cell culture. A scratch was mimicked in co-culture with keratinocytes and <i>R. mucosa</i> from either healthy or atopic dermatitis individuals. Keratinocytes co-cultured with <i>R. mucosa</i> from healthy individuals proliferated and “healed” the scratch faster, whereas co-cultures with <i>R. mucosa</i> from atopic dermatitis individuals did not affect keratinocyte growth. Exploring transcriptomics, quantitative enzymatic comparison, and metabolomics between <i>R. mucosa</i> from individuals with and without atopic dermatitis, the authors found differences in each experimental approach regarding glycerophospholipid production. In cell culture, keratinocytes were treated with lipids isolated from <i>R. mucosa</i> of healthy individuals. Similar increases in keratinocyte growth were observed when cells were treated with lipids or cultured with <i>R. mucosa</i> from healthy individuals. However, when keratinocytes were treated with a lipase after lipid addition, the increase in growth was ablated (Myles et al., 2020). <span style="color:black">The podcast hosts presented a very unique and impactful study detailing basic research and clinical trial data in a fun and interactive format for all audiences. </span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">References</span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Myles, I. A., Castillo, C. R., Barbian, K. D., Kanakabandi, K., Virtaneva, K., Fitzmeyer, E., ... &amp; Datta, S. K. (2020). Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair. Science translational medicine, 12(560).</span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Schmidt, M., Swanson, M., Schaechter, E., Racaniello, V. (2020). <i>Two microbes you might not know</i> (No. 226). <a href="https://www.microbe.tv/twim/twim-226/" style="color:#0563c1; text-decoration:underline">https://www.microbe.tv/twim/twim-226/</a></span></span></p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Clostridium%20bonelium.png?itok=9GH1N30r" width="576" height="382" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=7" hreflang="und">TWiM</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Sun, 07 Feb 2021 21:56:56 +0000 lacydb1 309 at https://www.vumc.org/lacy-lab The Story of Antibiotics and Bacterial Resistance https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/story-antibiotics-and-bacterial-resistance <span class="field field--name-title field--type-string field--label-hidden">The Story of Antibiotics and Bacterial Resistance</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Sat, 02/06/2021 - 12:38</span> <a href="/lacy-lab/blog-post-rss/308" class="feed-icon" title="Subscribe to The Story of Antibiotics and Bacterial Resistance"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Abbie Weit</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="text-align:justify; text-indent:.5in"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Arial&quot;,sans-serif"><span lang="EN" style="font-size:12.0pt" xml:lang="EN"><span style="font-family:&quot;Times New Roman&quot;,serif">In the lecture taught by Dr. James Cassat, our class learned about the history of antibiotic discovery. The timeline started with penicillin which was discovered by Alexander Fleming. After a vacation to Scotland in 1928, Fleming returned to his lab to find a plate of staphylococcus that had been left out on the bench. The plate was contaminated with a mold that he hypothesized was secreting something that killed the staph. Since it was difficult to extract the secretion from the plate, Professors Florey, Chain, and Heatley figured out the technique and resources to do so successfully. This led to major use of penicillin in treating infections in World War II soldiers.<sup>1,3</sup> Penicillin also started the golden age of antibiotic discovery. Discoveries that followed included prontosil by Gerhard Domagk who successfully treated his daughter with sepsis. The Soviets isolated streptomycin from soil which was the first antibiotic that was active against tuberculosis. Another antibiotic extracted from a soil sample was tetracycline which was used to treat fevers, skin infections, and respiratory infections.<sup>2</sup> This explosion of antibiotics continued until around the 1990s when there was what Dr. Cassat referred to as the “discovery void of antibiotics”. Dr. Cassat believes we may be entering a second golden age of antibiotics, yet they are not as widely used and profitable as before due to the phenomenon of antibiotic resistance. </span></span></span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Arial&quot;,sans-serif"><span lang="EN" style="font-size:12.0pt" xml:lang="EN"><span style="font-family:&quot;Times New Roman&quot;,serif">            Although antibiotics are a great resource for treatment of various infections, microorganisms quickly develop a defense or resistance to these drugs making them less effective. The main cause of antibiotic resistance is overuse of antibiotics.<sup>3</sup> This can occur spontaneously through mutations.<sup>4</sup> Also, genes are inherited or passed between non-relative bacteria which is a process called horizontal gene transfer.<sup>4</sup> Because resistance spreads so easily, it is crucial for physicians to only prescribe antibiotics when necessary. However, that is often not the case. In 2010, many U.S. states prescribed antibiotics more times than the number of people in the state.<sup>5</sup> Studies also show that antibiotic treatments are wrong or unnecessary in 30-50% of cases.<sup>3</sup> Antibiotic resistance is projected to cause ten million deaths by 2050 as noted by Dr. Cassat.<sup>6</sup> The best ways that physicians can decrease resistance is by not treating asymptomatic infections<sup>4</sup> and exhausting all other treatment options before using antibiotics. </span></span></span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Arial&quot;,sans-serif"><span lang="EN" style="font-size:12.0pt" xml:lang="EN"><span style="font-family:&quot;Times New Roman&quot;,serif">            A major caveat of physicians using less antibiotics is the resulting decrease in revenue for suppliers. Dr. Cassat stated that many of these therapeutics sit on hospital shelves for just periodic, necessary cases which results in little demand for the product. Therefore, it is quite hard for pharmaceutical companies to make profit on antibiotic treatments.<sup>6</sup> This prevents companies from pursuing opportunities for developing new antibiotics leading to a lack of progression in this field. Dr. Cassat believes that academic research of antibiotics is at the level of a second golden age. However, it is difficult to get these exciting developments to reach the clinic due to companies not wanting the financial risk. I firmly agree with Dr. Cassat’s view that federal and state funding should be used to support companies aiming to bring these drugs to market so that physicians may continue using antibiotics sparingly. Therefore, new antibiotics will continue to be produced yet we can slow down future antibiotic resistant-related deaths simultaneously. </span></span></span></span></span></p> <ol> <li style="margin-left:8px; text-align:justify"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Arial&quot;,sans-serif"><span lang="EN" style="font-size:12.0pt" xml:lang="EN"><span style="font-family:&quot;Times New Roman&quot;,serif">Sengupta, S., Chattopadhyay, M. K., &amp; Grossart, H. P. (2013). The multifaceted roles of antibiotics and antibiotic resistance in nature. Frontiers in Microbiology. Frontiers Research Foundation. </span></span><a href="https://doi.org/10.3389/fmicb.2013.00047" style="color:blue; text-decoration:underline"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#1155cc">https://doi.org/10.3389/fmicb.2013.00047</span></span></span></a></span></span></span></li> <li style="margin-left:8px; text-align:justify"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Arial&quot;,sans-serif"><span lang="EN" style="font-size:12.0pt" xml:lang="EN"><span style="font-family:&quot;Times New Roman&quot;,serif">Tetracycline: MedlinePlus Drug Information. (n.d.). Retrieved January 13, 2021, from </span></span><a href="https://medlineplus.gov/druginfo/meds/a682098.html" style="color:blue; text-decoration:underline"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#1155cc">https://medlineplus.gov/druginfo/meds/a682098.html</span></span></span></a></span></span></span></li> <li style="margin-left:8px; text-align:justify"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Arial&quot;,sans-serif"><span lang="EN" style="font-size:12.0pt" xml:lang="EN"><span style="font-family:&quot;Times New Roman&quot;,serif">Ventola, C. L. (2015). The antibiotic resistance crisis: causes and threats. P &amp; T Journal, 40(4), 277–283. <a href="https://doi.org/Article">https://doi.org/Article</a></span></span></span></span></span></li> <li style="margin-left:8px; text-align:justify"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Arial&quot;,sans-serif"><span lang="EN" style="font-size:12.0pt" xml:lang="EN"><span style="font-family:&quot;Times New Roman&quot;,serif">Read, A. F., &amp; Woods, R. J. (2014). Antibiotic resistance management. Evolution, Medicine and Public Health, 2014(1), 147. </span></span><a href="https://doi.org/10.1093/emph/eou024" style="color:blue; text-decoration:underline"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#1155cc">https://doi.org/10.1093/emph/eou024</span></span></span></a></span></span></span></li> <li style="margin-left:8px; text-align:justify"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Arial&quot;,sans-serif"><span lang="EN" style="font-size:12.0pt" xml:lang="EN"><span style="font-family:&quot;Times New Roman&quot;,serif">Gross, M. (2013). Antibiotics in crisis. Current Biology, 23(24). </span></span><a href="https://doi.org/10.1016/j.cub.2013.11.057" style="color:blue; text-decoration:underline"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">https://doi.org/10.1016/j.cub.2013.11.057</span></span></a></span></span></span></li> <li style="margin-left:8px; text-align:justify"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Arial&quot;,sans-serif"><span lang="EN" style="font-size:12.0pt" xml:lang="EN"><span style="font-family:&quot;Times New Roman&quot;,serif">Plackett, B. (2020, October 1). Why big pharma has abandoned antibiotics. <i>Nature</i>. NLM (Medline). <a href="https://doi.org/10.1038/d41586-020-02884-3">https://doi.org/10.1038/d41586-020-02884-3</a></span></span></span></span></span></li> </ol> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Abbie.png?itok=5lj4K63F" width="576" height="487" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=19" hreflang="und">Lecture Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Sat, 06 Feb 2021 18:38:42 +0000 lacydb1 308 at https://www.vumc.org/lacy-lab A Whiff of Taxonomy – The Apicomplexa by Moselio (Elio) Schaechter https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/whiff-taxonomy-apicomplexa-moselio-elio-schaechter <span class="field field--name-title field--type-string field--label-hidden">A Whiff of Taxonomy – The Apicomplexa by Moselio (Elio) Schaechter</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Sat, 02/06/2021 - 12:26</span> <a href="/lacy-lab/blog-post-rss/307" class="feed-icon" title="Subscribe to A Whiff of Taxonomy – The Apicomplexa by Moselio (Elio) Schaechter"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">CVRVC</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Apicomplexa are a phylum of parasitic alveolates that get their name from <span style="background:white">the presence of the apical complex. The apical complex consists of many microtubules and secretory organelles, such as the </span>micronemes<span style="background:white"> and the </span>rhoptries<span style="background:white">. Additionally, an organelle, the apicoplast, contains its own DNA and is considered a derivative of chloroplasts in plants. Micronemes secrete proteins known as microneme proteins (MICs) which are vital in the initial stages of host cell invasion by parasites (Foroutan 2018). Rhoptries undergo exocytosis upon host cell invasion and their proteins are involved in creating the moving junction that propels the parasite in the cell and in building the parasitophorous vacuole in which the parasite develops (Dubremetz, 2007)</span>.</span></span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Apicomplexa’s main goals are to reproduce rapidly and produce a large amount of progeny to exist for a long time, and to successfully enter a host organism. They achieve this by asexual reproduction based on where new parasites are formed. When daughter parasites are formed inside the parent the process is called endodyogeny/endopolygeny, while budding from the mother plasmalemma (cell membrane) is called schizogony. When Apicomplexa species enter a host organism, they can cause various life-threatening diseases to human and animals.</span></span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Apicomplexan parasites <span style="background:white">such as </span><i>Toxoplasma gondii, Plasmodium</i><span style="background:white"> spp, and </span><i>Cryptosporidium </i>are leading causes of human and livestock diseases—like toxoplasmosis, malaria, and severe diarrhea, respectively (Checkley, 2015).</span></span></span><i><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black"> Toxoplasma gondii </span></span></span></i><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">is an intracellular protozoan parasite of global importance that can remarkably infect, survive, and replicate in nearly all mammalian cells (Lima, 2019). Many infections caused by <i>Toxoplasma gondii</i> are asymptomatic, but can be very life-threatening infections. According to the CDC, <span style="background:white">toxoplasmosis is a leading cause of death caused by foodborne illness in the United States where more than 40 million men, women, and children in the U.S. carry the </span><em><span style="font-family:&quot;Calibri&quot;,sans-serif">Toxoplasma</span></em> <span style="background:white">parasite. </span>Temperature is a key factor influencing the invasion and proliferation of <i>Toxoplasma gondii</i> in fish cells (Yang, 2020). <i><span style="background:white">Plasmodium spp</span></i><span style="background:white"> have infected more than 300 to 500 million individuals worldwide, and 1.5 to 2.7 million people a year, most of whom are children, die from the infection (Garcia, 2010). M</span><span style="font-family:&quot;Calibri&quot;,sans-serif">alaria</span> <span style="background:white">is transmitted by mosquitoes carrying a specific parasite. People with malaria often experience fever, chills, and flu-like illness. Malaria was found to be caused by the 4 most common Plasmodium spp that infect humans, <i>P. vivax</i>, <i>P. ovale</i>, <i>P. malariae</i>, and <i>P. falciparum </i>(Garcia, 2010). The </span><em><span style="font-family:&quot;Calibri&quot;,sans-serif">CDC described Cryptosporidium</span></em></span></span></span><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black"> as a parasite </span></span></span><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">that infects both animals and humans. The parasite is protected by an outer shell that allows it to survive outside the body for long periods of time and makes it very tolerant to chlorine disinfection, hence, making water an easy spreader.</span></span></span></span></span><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black"> Apicomplexan diseases are life-threatening, and infections should be ultimately avoided. In case of infection, treatments such as antibiotics, should be utilized to prevent death. </span></span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><b><u><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">References</span></span></span></u></b></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Checkley W, White AC, Jaganath D, Arrowood MJ, Chalmers RM, Chen XM, Fayer R, Griffiths JK, Guerrant RL, Hedstrom L, et al. A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium. Lancet Infect Dis. 2015; 15:85–94. </span></span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:14.0pt"><span style="background:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Dubremetz, JF. 2007. </span></span></span></span><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Rhoptries are major players in <i>Toxoplasma gondii</i>invasion and host cell interaction. <span style="background:white">Cellular</span> <span style="background:white">Microbiology</span> <span style="background:white">(2007)</span> 9<span style="background:white">(4),</span> <span style="background:white">841–848</span> </span></span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:14.0pt"><span style="background:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Foroutan M, Zaki L, Ghaffarifar F. 2018. Recent progress in </span></span></span></span><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">microneme<span style="background:white">-based vaccines development against Toxoplasma gondii. Clin Exp Vaccine Res. 7(2):93-103. doi: 10.7774/cevr.2018.7.2.93.</span></span></span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Garcia, LS. 2010. Malaria. Clinical Lab Med. 30(1):93-129.</span></span></span><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">doi: 10.1016/j.cll.2009.10.001.</span></span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Lima, TS and Lodoen, MB. 2019. Mechanisms of Human Innate Immune Evasion by <i>Toxoplasma gondii. </i><i>Front. Cell. Infect. Microbiol. 9:103. doi: 10.3389/fcimb.2019.00103 </i></span></span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:14.0pt"><span style="background:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Yang Y, Yu SM, Chen K, Hide G, Lun ZR, Lai DH. 2020. </span></span></span></span><span style="font-size:14.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Temperature is a key factor influencing the invasion and proliferation of Toxoplasma gondii in fish cells. <span style="background:white">Exp Parasitol.217:107966. doi: 10.1016/j.exppara.2020.107966.</span></span></span></span></span></span></p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Carlan.png?itok=18_FGuN1" width="446" height="482" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=7" hreflang="und">TWiM</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Sat, 06 Feb 2021 18:26:06 +0000 lacydb1 307 at https://www.vumc.org/lacy-lab “Staying Healthy: Hide Your Metal” https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/staying-healthy-hide-your-metal <span class="field field--name-title field--type-string field--label-hidden">“Staying Healthy: Hide Your Metal”</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Wed, 02/03/2021 - 08:19</span> <a href="/lacy-lab/blog-post-rss/306" class="feed-icon" title="Subscribe to “Staying Healthy: Hide Your Metal”"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Eki</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="text-align:justify; text-indent:.5in; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:106%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="line-height:106%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Earlier this month, in the class lecture, "Staying Healthy: Hide Your Metal", Dr. Jennifer Gaddy introduced the importance of metal ion homeostasis, an important balance in which cells must keep an adequate level of metals that serve as cofactors for various enzymes and other proteins, but also, avoid metal ion intoxication (</span></span></span></span><span style="font-size:12.0pt"><span style="background:white"><span style="line-height:106%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Chandrangsu et al., 2017)</span></span></span></span></span><span style="font-size:12.0pt"><span style="line-height:106%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">. Metal ions are essential for several cellular processes such as cellular growth, cellular respiration, and stress responses. The vertebrate host serves as a rich source of nutrient metals for all microorganisms, which have a strict growth requirement for transition metals, which is around 10 <sup>-6</sup> – 10 <sup>-8 </sup>M. In addition to cellular growth, bacteria require cofactors for stress responses. When bacteria encounter environmental stressors, cytoplasmic enzymes are essential for repressing the stressors. The host vertebrate's common stressors are reactive oxygen species (ROS), which are highly reactive molecules that are generated during mitochondrial oxidative metabolism. However, several enzymes used to break down harmful ROS are called superoxide dismutase (SOD), and they use an array of metal cofactors such as manganese, iron, zinc, and copper. In the case of the finite number of metals, SOD is not functional and cannot detoxify ROS. Accumulation of ROS can be detrimental for the host and may damage nucleic acids, proteins, and other cellular components. Another topic covered during the lecture was cellular respiration, a set of metabolic reactions and processes in which cells convert chemical energy from oxygen or nutrients into adenosine triphosphate (ATP).  During respiration, the electrons are transferred by reduction/oxidation or by cytochromes oxidase complex via catalysis, in which the free energy generated by electron transfer is utilized by ATP synthase. The final step in the process is catalyzed by complex IV (cytochrome oxidase), where electrons are transferred from cytochrome c to the molecular oxygen, which serves as the terminal electron acceptor in aerobic respiration. Cytochromes have various cofactors necessary for cellular respiration, such as ferric sulfur clusters, iron-sulfur clusters, copper centers, and the main requirement is heme (</span></span></span></span><span style="font-size:12.0pt"><span style="line-height:106%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Landolfo, 2008)</span></span></span></span><span style="font-size:12.0pt"><span style="line-height:106%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">.</span></span></span></span></span></span></span></p> <p style="text-align:justify; text-indent:.5in; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Vertebrate immune systems developed revolutionary defense mechanisms in order to protect invading pathogens. Nutritional immunity is when the host exploits microbial requirements for transition metals by sequestering them to limit pathogenicity during the infection. Concentrations of metals, such as iron and zinc, decline fast during the infection, and the reason for it is to starve invading pathogens of these essential elements (Begg, 2019). Nutritional immunity is regulated by several proteins such as S-100A, transferrin, lactoferrin, heme, and hemoglobin. The large S-100A family of calcium-binding proteins are found in vertebrates and are important for defense against infection since many S-100A proteins have antimicrobial properties. One of the best-studied is calprotectin (S100A8/A9), which makes up approximately 40% of the neutrophil cytoplasm's protein composition and can bind zinc, manganese, iron, and copper. Another vital protein, S-100A12, also known as calgranulin C, binds both zinc and copper and is involved in generating superoxide species. Studies have shown that genetic mutation in the metal-binding sites of S-100A proteins disrupts proteins' antimicrobial activity. Lactoferrin and transferrin, dual-lobed multifunctional glycoproteins found in a vertebrate, bind and mediate the transport of iron through the blood plasma. Increasing concentrations of lactoferrin and transferrin inhibit the growth of various pathogens over time. Most of the body's iron is found in the Red Blood Cells (RBCs), specifically in protein hemoglobin, which is essential for transferring oxygen in the blood. Hemoglobin comprises four polypeptide chains, two alpha and two beta chains, with each chain attached to a heme group composed of a porphyrin ring attached to an iron atom. </span></span></span></span></span></span></p> <p style="text-align:justify; text-indent:.5in; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:106%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="line-height:106%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">To bypass metal starvation, microorganisms deploy metal piracy systems, such as siderophores, zincophores, and cuprophores, to exploit the transition metals. Siderophores, zincophores, and cuprophores are low molecular weight compounds that can bind transition metals with high affinity. Deployment of toxins, such as hemolytic toxins, is another mechanism to bypass metal starvation. Hemolytic toxins destroy RBCs and release free hemoglobin, which is then degraded by hemoglobin protease to release heme, following secretion of hemophores, which capture heme and shuttle it across the membrane. Additionally, in response to zinc starvation, bacteria can alter their outer membrane, which causes biofilm formation. Lastly, Dr. Gaddy concluded the lecture by talking about metal toxicity. Metal toxicity can cause protein denaturation, disrupt the cell membrane, inhibit transcription and cell division, and inhibit enzyme activity. One of the most common deleterious effects of metal toxicity is mismetallation, which results in enzyme activity inhibition because the wrong ion has replaced the correct cofactor. Bacteria respond to metal toxicity by deploying efflux pumps to exclude metal ions out of the cell.</span></span></span></span> <span style="font-size:12.0pt"><span style="line-height:106%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black"> Recent studies have shown that bacteria can highjack host metal-binding proteins to help mitigate metal toxicity.</span></span></span></span></span></span></span></p> <p style="margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">References</span></span></span></span></span></span></p> <ol> <li style="margin-left:8px"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Chandrangsu, P., Rensing, C. &amp; Helmann, J. Metal homeostasis and resistance in bacteria. <i>Nat Rev Microbiol</i> <b>15, </b>338–350 (2017). <a href="https://doi.org/10.1038/nrmicro.2017.15">https://doi.org/10.1038/nrmicro.2017.15</a></span></span></span></span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Begg SL. The role of metal ions in the virulence and viability of bacterial pathogens. Biochem Soc Trans. 2019 Feb 28;47(1):77-87. doi: 10.1042/BST20180275. Epub 2019 Jan 9. PMID: 30626704.</span></span></span></span></span></span></span></li> <li style="margin-left:8px"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Sara Landolfo, Huguette Politi, Daniele Angelozzi, Ilaria Mannazzu, ROS accumulation and oxidative damage to cell structures in Saccharomyces cerevisiae wine strains during fermentation of high-sugar-containing medium, Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1780, Issue 6, 2008, Pages 892-898, ISSN 0304-4165, <a href="https://doi.org/10.1016/j.bbagen.2008.03.008">https://doi.org/10.1016/j.bbagen.2008.03.008</a>.</span></span></span></span></span></span></li> </ol> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Eki.png?itok=6WtnpISV" width="240" height="254" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=19" hreflang="und">Lecture Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Wed, 03 Feb 2021 14:19:35 +0000 lacydb1 306 at https://www.vumc.org/lacy-lab VI4 Seminar, 1/14/21, Dr. Carolyn Ibberson https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/vi4-seminar-11421-dr-carolyn-ibberson <span class="field field--name-title field--type-string field--label-hidden">VI4 Seminar, 1/14/21, Dr. Carolyn Ibberson</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Tue, 01/26/2021 - 19:44</span> <a href="/lacy-lab/blog-post-rss/304" class="feed-icon" title="Subscribe to VI4 Seminar, 1/14/21, Dr. Carolyn Ibberson"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">KayLee Steiner</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">            This week, I attended a seminar from the VI4 at Vanderbilt University Medical Center, which hosted Dr. Carolyn Ibberson from Georgia Institute of Technology. She is a current faculty candidate for Vanderbilt and her presentation was titled “Insights into<i> S. aureus </i>infection physiology through-omics approaches.” <i>Staphylococcus aureus </i>is a common bacterial pathogen that is found virtually on all skin in populations and it is important to study to understand how bacteria establish and persist in infections. It is also important to acknowledge that <i>S. aureus</i> is not the only common bacteria found on the skin. Because of this, Dr. Ibberson uses an “ecosystem” approach to study pathogenesis by using several types of -omics approaches in infection sites such as chronic wound infections, abscesses, and osteomyelitis.</span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">            With Dr. Ibberson’s research, she has been analyzing essential genes in <i>S. aureus</i> through -omics approaches in hopes to develop therapeutic targets. With her research, she found that the specific infection site of <i>S. aureus</i> impacts the essential genome. Thirty-nine genes were found to be shared in the three infection sites, however, more genes were found to be unique to each site than what were shared. In a separate part of her research, she studies how co-infection with <i>Pseudomonas aeruginosa </i>changes the essential genome. She found that 6% of the genome changed, with a quarter of the genes that were previously required in each infection no longer needed. I thought this was an interesting finding and wondered why this could happen. Possibly one bacterium is compensating for the other in producing proteins and compounds to persist in the infection site. This research led her to study <i>S. aureus </i>with respect to infections in Cystic Fibrosis patients. By analyzing the transcriptomes, she was able to determine that the transcriptomes are different in human infections than with <i>in vitro</i> conditions. The -omics technologies that Dr. Ibberson used were vital to her research and understanding <i>S. aureus </i>infection physiology. </span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">            While listening to the seminar, I realized how important sequencing and the -omics technologies are for current studies. Only seventeen years ago the Human Genome Project was finished with the first complete human genome which cost millions of dollars [1]. Today, sequences can be determined with less time and money, which aids researchers to utilize these technologies. Also, sequencing many organisms at once has been made possible to better understand environments like human skin, cells, and soil. Technologies such as genomics, transcriptomics, proteomics, metabolomics, etc. are greatly utilized for these studies and also greatly help clinical researchers [2]. Insights can be made into diagnosing diseases and also help inform doctors about the correct treatment plan, especially relevant for cancer patients. In addition, sequencing and -omics technologies have greatly aided microbiome research to create a more holistic view of the environment [3], which greatly helps researchers and their data, as shown by Dr. Ibberson’s research. </span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">References</span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">[1] Shendure J. et.al. (2017). DNA sequencing at 40: Past, present, and future. <i>Nature Review</i>. doi:10.1038/nature24286</span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">[2] Karczewski K, Snyder MP. (2018). Integrative omics for health and disease. <i>Nature Reviews, Genetics.</i> 19: 299-310</span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">[3] Knight R. et.al. (2018). Best practices for analyzing microbiomes. <i>Nature Review Microbiology. </i>16(7). <span style="color:#212121">DOI: </span><a href="https://doi.org/10.1038/s41579-018-0029-9" target="_blank"><span style="color:#0071bc">10.1038/s41579-018-0029-9</span></a></span></span></p> <p> </p> <p> </p> <p align="center" style="text-align:center"> </p> <p> </p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Steiner_Headshot.png?itok=pYH3L3bk" width="268" height="269" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=19" hreflang="und">Lecture Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Wed, 27 Jan 2021 01:44:19 +0000 lacydb1 304 at https://www.vumc.org/lacy-lab A look at disease vectors: The mosquito https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/look-disease-vectors-mosquito <span class="field field--name-title field--type-string field--label-hidden">A look at disease vectors: The mosquito</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Mon, 01/25/2021 - 17:16</span> <a href="/lacy-lab/blog-post-rss/303" class="feed-icon" title="Subscribe to A look at disease vectors: The mosquito"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Jordyn Sanner</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p class="MsoNoSpacing" style="text-indent:.5in"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">Insects inhabit our world, acting as agricultural pollinators and pests, as well as vectors of diseases. As common disease vectors, mosquitoes have been identified as one of the deadliest organisms in the world [1]. In a recent lecture, Dr. Julián Hillyer took us on a journey through the mosquito, assessing how the mosquito acts as a disease vector and identifying pathogens transmitted by this common insect.</span></span></span></span></p> <p class="MsoNoSpacing"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">            Commonly, mosquitoes acquire pathogens via horizontal transmission while blood-feeding on an intermediary host. However, just because a pathogen enters the mosquito host does not mean that it will be transmitted to a secondary human host. The ability of a mosquito to transmit disease is defined by vector competence, which is influenced by internal factors such as genetics, behavior, and the microbiome, or external factors, such as external temperature, host density, and predator density [2]. Vectoral competence is just one component of the vectorial capacity equation, which is used to define the number of secondary cases of infection that arise from each primary infection [3]. This equation accounts for host factors such as vector density, vector biting rate, and vector survival and adjusts for pathogen factors such as the extrinsic incubation period (EIP) [3]. This equation allows humans to define the magnitude of mosquito disease transmission.</span></span></span></span></p> <p class="MsoNoSpacing"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">            One of the primary parasites transmitted by mosquitoes is <i>Plasmodium</i>, which causes malaria in humans. Belonging to the phylum Apicomplexa, these parasitic protozoa possess an apical complex which is used to invade cells [4]. Malaria infections are most prevalent in tropical regions of the world, such as Africa, South America, and Southern Asia. Five species of <i>Plasmodium</i> infect humans and lead to disease. These species all share a common life cycle and can only infect mosquitoes via a blood meal while in the gametocyte stage. Once in the mosquito, sexual reproduction occurs and forms the zygote [4]. The zygote transforms to its motile stage, an ookinete, and migrates out of the midgut, where it becomes an oocyst. The migration continues to the salivary glands, where the pathogen enters the sporozoite stage of development, 7-10 days after entering the mosquito [4]. Sporozoites are transferred to humans via saliva at the mosquito’s next blood meal. In humans, sporozoites travel to the liver to infect hepatocytes, where the pathogen undergoes asexual reproduction, leading to cell lysis and the release of hundreds of merozoites [4]. Merozoites then infect erythrocytes and undergo asexual reproduction within the cells [4]. The red blood cells lyse, resulting in anemia, and hundreds of pathogens are released into the body to further the infection. The cycle of cells lysing also corresponds to the fever cycles of malaria symptoms.</span></span></span></span></p> <p class="MsoNoSpacing"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">            Mosquitoes are also known to transmit filarial nematodes, which block the lymphatics in humans. Although not deadly, this pathogen can permanently incapacitate people and may lead to ‘elephantiasis.’ This pathogen is commonly found in tropical, developing countries and is acquired by the mosquito during a blood meal. Within the mosquito, the pathogen exits the gut to invade the flight muscles, where it molts from larval stage 1 to stage 3 [5]. From there, it migrates to the mosquito’s mouth parts, where it can crawl into the wound during the mosquito’s next blood meal [5]. Once in the human, the parasite seeks the lymphatics and molts [5]. If males and females are present, they mate and further the infection.</span></span></span></span></p> <p class="MsoNoSpacing"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">            Many viruses, such as Zika, Dengue, and Chikungunya, are also commonly vectored by mosquitoes. However, any pathogen transmitted by the mosquito must overcome barriers to infection within the insect. Mosquitoes illicit a strong immune response after acquiring a pathogen because they experience the infection, too. Dr. Hillyer’s lab studies mosquito physiology, specifically focusing on the combined effects of the circulatory and immune systems of the mosquito to understand the molecular components of the mosquito’s immune response to infection. If we understand the biology of the vector, we may be able to identify new ways to control diseases transmitted by this common insect.</span></span></span></span></p> <p class="MsoNoSpacing"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">References:</span></span></span></span></p> <ol> <li class="MsoNoSpacing" style="margin-left:8px"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Čirjak, A., 2020. <i>Why Mosquitoes Are The Deadliest Animals On The Planet</i>. [online] WorldAtlas. Available at: </span></span></span></span><a href="https://www.worldatlas.com/articles/why-mosquitoes-are-the-deadliest-animals-on-the-planet.html" style="color:#0563c1; text-decoration:underline"><span style="font-size:12.0pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif">https://www.worldatlas.com/articles/why-mosquitoes-are-the-deadliest-animals-on-the-planet.html</span></span></span></a></span></span></li> <li class="MsoNoSpacing" style="margin-left:8px"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span lang="FR" style="font-size:12.0pt" xml:lang="FR"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#303030">Lefèvre, T., Vantaux, A., Dabiré, K. R., Mouline, K., &amp; Cohuet, A. (2013). </span></span></span></span><span style="font-size:12.0pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#303030">Non-genetic determinants of mosquito competence for malaria parasites. <i>PLoS pathogens</i>, <i>9</i>(6), e1003365. </span></span></span></span><a href="https://doi.org/10.1371/journal.ppat.1003365" style="color:#0563c1; text-decoration:underline"><span style="font-size:12.0pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif">https://doi.org/10.1371/journal.ppat.1003365</span></span></span></a></span></span></li> <li class="MsoNoSpacing" style="margin-left:8px"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#222222">Shaw, W.R., Catteruccia, F. Vector biology meets disease control: using basic research to fight vector-borne diseases. <i>Nat Microbiol</i> <b>4, </b>20–34 (2019). </span></span></span></span><a href="https://doi.org/10.1038/s41564-018-0214-7" style="color:#0563c1; text-decoration:underline"><span style="font-size:12.0pt"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif">https://doi.org/10.1038/s41564-018-0214-7</span></span></span></a></span></span></li> <li class="MsoNoSpacing" style="margin-left:8px"><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">Aly, A., Vaughan, A.M., &amp; Kappe, S. Malaria Parasite Development in the Mosquito and Infection of the Mammalian Host. Annual Review of Microbiology 2009 63:1, 195-221</span></span></span></span></li> <li class="MsoNoSpacing" style="margin-left:8px"><span style="font-size:12.0pt"><span style="background:white"><span style="line-height:107%"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:#222222">Cross JH. Filarial Nematodes. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 92. Available from: <a href="https://www.ncbi.nlm.nih.gov/books/NBK7844">https://www.ncbi.nlm.nih.gov/books/NBK7844</a></span></span></span></span></span></li> </ol> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/JordynSanner.png?itok=jqrCXWoj" width="442" height="506" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=19" hreflang="und">Lecture Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Mon, 25 Jan 2021 23:16:25 +0000 lacydb1 303 at https://www.vumc.org/lacy-lab Turducken antibiotics https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/turducken-antibiotics <span class="field field--name-title field--type-string field--label-hidden">Turducken antibiotics</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Sun, 01/24/2021 - 18:14</span> <a href="/lacy-lab/blog-post-rss/302" class="feed-icon" title="Subscribe to Turducken antibiotics"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Julissa Burgos</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:Times"><span style="color:black">In the podcast “This Week in Microbiology” the hosts Vincent Racaniello and Michael Schmidt discussed a scientific paper on a novel synthetic dual drug called sideromycin that is used to combat Gram-negative bacteria. The lack of antibiotics against Gram-negative bacteria is a huge health concern, and there is a need to find novel ways to eliminate pathogens.  Gram-negative bacteria have an outer membrane that makes it difficult for antibiotics to cross into, and many species also secrete </span></span><span style="font-family:Times"><span style="color:#212121">β-lactamases which degrade β-lactam antibiotics that target peptidoglycan cell wall synthesis. The authors of the paper describe the synthesis of a dual drug conjugate that has three components (a siderophore, a β-lactam, and an antibiotic). The first is the siderophore which is an iron-chelating compound secreted by bacteria to transport iron across membranes. The siderophore is linked to cephalosporin, a β-lactam antibiotic that is cleaved when it enters the periplasm by β-lactamases. Finally, the third component is oxazolidine a known Gram-positive antibiotic that inhibits protein synthesis. All together the siderophore is used to transport the antibiotic through the outer membrane, and then in the periplasm, β-lactamases cleave oxazolidine from cephalosporin, releasing the antibiotic to perform its function in Gram-negative bacteria. </span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:Times"><span style="color:black">The authors tested sideromycin in <i>Acinetobacter baumannii, </i>a Gram-negative bacterium that has become resistant to </span></span><span style="font-family:Times"><span style="color:#212121">β-lactamases. Bacteria need iron for their physiological processes, and they secrete the siderophores to obtain more iron from their environment. In the experiments with sideromycin, the bacteria will take in the siderophore with the antibiotic linked to it.  In the podcast, the hosts mention how surprising it is that the bacteria are tricked into taking the antibiotic when it is sequestering iron. I also agree with how clever it is to trick the bacteria by using their own mechanisms. Once the drug passes the outer membrane, the antibiotic portion of the drug, oxazolidine, will be close enough to inhibit protein synthesis in </span></span><span style="font-family:Times"><span style="color:black">the bacteria</span></span><span style="font-family:Times"><span style="color:#212121">. Oxazolidine is known to target Gram-positive bacteria but it has failed to eliminate Gram-negative bacteria in the past because it cannot get across the outer membrane. However, in this paper, they showed the antibiotic to be active against </span></span><i><span style="font-family:Times"><span style="color:black">A. baumannii </span></span></i><span style="font-family:Times"><span style="color:black">when the bacteria were treated with the dual drug sideromycin. </span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:Times"><span style="color:black">In my opinion, this novel drug is a breathtaking discovery given the high rates of antibiotic resistance in the world we live in today. This paper shows why it is so important to understand the mechanisms involved in bacterial infections and learn new areas where we can target with antibiotics or other therapeutics. In the paper, the authors show a novel way of introducing known antibiotics that target Gram-positive bacteria to now target Gram-negative bacteria. </span></span><span style="font-family:Times"><span style="color:#212121">The hosts of the podcast also commented on how they</span></span><span style="font-family:Times"><span style="color:black"> hope the process of this drug being approved by the FDA is faster knowing </span></span><span style="font-family:Times"><span style="color:#212121">cephalosporin and oxazolidine are already approved. </span></span><span style="font-family:Times"><span style="color:black">This type of drug delivery system opens a new door for the exploration of known antibiotics on multi-resistant bacteria and the knowledge of how to use a bacterium’s own mechanisms of action for drug delivery.</span></span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:Times">References: </span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-family:Times">Racaniello, V., Schmidt, M. (Hosts). (2018, Oct 31). Turducken antibiotics. This Week in Microbiology [Audio podcast]. Retrieved from </span><a href="https://asm.org/Podcasts/TWiM" style="color:#0563c1; text-decoration:underline"><span style="font-family:Times">https://asm.org/Podcasts/TWiM</span></a><span style="font-family:Times">.</span></span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="background:white"><span style="font-family:Times"><span style="color:#212121">Liu, R., Miller, P. A., Vakulenko, S. B., Stewart, N. K., Boggess, W. C., &amp; Miller, M. J. (2018). A Synthetic Dual Drug Sideromycin Induces Gram-Negative Bacteria to Commit Suicide with a Gram-Positive Antibiotic. </span></span></span><i><span style="font-family:Times"><span style="color:#212121">Journal of medicinal chemistry</span></span></i><span style="background:white"><span style="font-family:Times"><span style="color:#212121">, </span></span></span><i><span style="font-family:Times"><span style="color:#212121">61</span></span></i><span style="background:white"><span style="font-family:Times"><span style="color:#212121">(9), 3845–3854. </span></span></span></span></span></p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Julissa.png?itok=AAIm-lPZ" width="414" height="576" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=7" hreflang="und">TWiM</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Mon, 25 Jan 2021 00:14:09 +0000 lacydb1 302 at https://www.vumc.org/lacy-lab Let’s Get Our Hands Dirty https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/lets-get-our-hands-dirty <span class="field field--name-title field--type-string field--label-hidden">Let’s Get Our Hands Dirty </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Sat, 01/16/2021 - 18:00</span> <a href="/lacy-lab/blog-post-rss/301" class="feed-icon" title="Subscribe to Let’s Get Our Hands Dirty "> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Ryan Fansler</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The rise of antibiotic resistance constitutes a very real and growing global health threat.   Between 2000 and 2020, only 24 new antibiotics were approved by the FDA, an alarming decrease from the 63 antibiotics approved in the preceding twenty years<sup>1</sup>. However, there is still hope for solutions to this crisis. In the November 5, 2020 episode, “Dirt Is Not Simple”, of the podcast series This Week in Microbiology, host Michael Schmidt discusses the possibility of a “second Golden Era of antibiotic discovery<sup>2</sup>.” This new era could stem from the newly appreciated biochemical diversity among Actinobacteria in the soil. Schmidt reviews the perspective article “Cryptic or Silent: The Known Unknowns, Unknown Knowns, and Unknown Unknowns of Secondary Metabolism” by Paul Hoskisson and Ryan Seipke<sup>3</sup>. Schmidt notes the authors’ optimism that the dawn of Next Generation Sequencing will allow for the identification of novel antibiotics from the largely untapped trove of natural products in the secondary metabolism of Streptomyces species in the soil-dwelling Actinobacteria phylum. Indeed, actinobacterial genome- mining has already uncovered biosynthetic gene clusters (BGCs) for over 11,000 previously unknown natural products<sup>4</sup>.</p> <p>Schmidt utilizes most of his time highlighting antibiotics successfully isolated from Actinobacterial natural products in the past. Schmidt thereby contextualizes the magnitude of this research area’s potential. Clavulanic acid, spectinomycin, ivermectin, amphotericin, nystatin, and chloramphenicol, all now developed drugs, are derived from Actinobacterial species. Schmidt emphasizes the complex structures of these natural products, pointing to the difficulty of synthetically developing these drugs in a lab: “Any organic chemist would break out into a sweat just looking at the precursors for these compounds. There’s no way you could actually make that.” He dives deep on the mechanism of clavulanic acid as one of the more interesting drugs to come out of the Actinobacteria treasure chest. Clavulanic acid is not itself an antibiotic. Instead, it enhances b-lactam antibiotics, such as penicillin, by inhibiting b-lactamase, an enzyme secreted by many bacterial species to protect their populations from b-lactams. Once clavulanic acid inactivates b-lactamase, b-lactam antibiotics can kill bacteria by inhibiting the synthesis of peptidoglycan, a key structural component of bacterial cell walls<sup>5</sup>. By noting the efficacy of just one such natural product isolated from Actinobacteria, Schmidt is effective in conveying wonder and excitement for the possibilities that could await in the 11,000 and growing natural products implied in the genomes of 830 Actinobacterial species.</p> <p>Schmidt finishes by acknowledging the enormous effort and manpower that will be required to translate the potential offered by Actinobacteria biochemical diversity into safe and effective antibiotics. Sequencing and computational methods uncovered the thousands of novel natural products, but the challenge remains for these compounds to be isolated, characterized, and analyzed for their potential as new antibiotics. Indeed, Hoskisson and Seipke admit that with such a wealth of data, even “prioritizing which BGCs to study presents a challenge in the field.” Numerous dedicated researchers will be needed to elucidate the properties of the Actinobacterial natural products. However, it is heartening to hear that a crisis as menacing as antibacterial resistance might be solved with nothing more than a handful of dirt and some hard work.</p> <p>References</p> <p>1.        Conly, J. M. &amp; Johnston, B. L. Where are all the new antibiotics? The new antibiotic paradox. Canadian Journal of Infectious Diseases and Medical Microbiology (2005) doi:10.1155/2005/892058.</p> <p>2.        Schmidt, M., Swanson, M., &amp; Racaniello, V. (2020). Dirt is not simple (No. 229). <a href="https://www.asm.org/Podcasts/TWiM/Episodes/Dirt-is-not-simple-TWiM-229">https://www.asm.org/Podcasts/TWiM/Episodes/Dirt-is-not-simple-TWiM-229</a></p> <p>3.        Hoskisson, P. A. &amp; Seipke, R. F. Cryptic or silent? The known unknowns, unknown knowns, and unknown unknowns of secondary metabolism. MBio (2020) doi:10.1128/mBio.02642-20.</p> <p>4.        Doroghazi, J. R. et al. Aroadmap for natural product discovery based on large-scale genomics and metabolomics. Nat. Chem. Biol. (2014) doi:10.1038/nCHeMBIO.1659.</p> <p>5.        Reading, C. &amp; Cole, M. Clavulanic acid: a beta lactamase inhibiting beta lactam from Streptomyces clavuligerus. Antimicrob. Agents Chemother. (1977) doi:10.1128/AAC.11.5.852.</p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Fansler.jpeg?itok=s0Iko8vV" width="432" height="576" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=7" hreflang="und">TWiM</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Sun, 17 Jan 2021 00:00:46 +0000 lacydb1 301 at https://www.vumc.org/lacy-lab How Clinicians are Combatting Antibiotic Resistance with Previously Avoided Therapies https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/how-clinicians-are-combatting-antibiotic-resistance <span class="field field--name-title field--type-string field--label-hidden">How Clinicians are Combatting Antibiotic Resistance with Previously Avoided Therapies</span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"><span lang="" about="/lacy-lab/users/lacydb1-0" typeof="schema:Person" property="schema:name" datatype="">lacydb1</span></span> <span class="field field--name-created field--type-created field--label-hidden">Tue, 02/11/2020 - 08:13</span> <a href="/lacy-lab/blog-post-rss/258" class="feed-icon" title="Subscribe to How Clinicians are Combatting Antibiotic Resistance with Previously Avoided Therapies"> RSS: <i class="fa fa-rss-square"></i> </a> <div class="field field--name-field-barista-posts-author field--type-string field--label-hidden field__item">Tomas Bermudez</div> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p style="text-indent:0in"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">            One of the unfortunate side effects of taking antibiotics to clear bacterial infection is its effect on the body’s microbiome. Antibiotics are generally nonselective in their targets; being put on a regimen of antibiotics can kill off an infection, but it will likely also cause harm to the beneficial bacteria of the patient (Dethlefsen et al., 2008). This creates openings in the niche environments of the microbiome, freeing up space that can be used for colonization in a subsequent infection. One of the organisms that takes advantage of this opening is <i>Clostridioides difficile</i>, a bacterium heavily associated with diarrheal disease that in severe cases can develop into colitis.  C. diff infections (CDIs) are almost always the result of an antibiotic treatment for some other infection. Seeing how this is the case, it is easy to picture the problem that many clinicians face when trying to treat a CDI. How do you treat a bacterial infection that was caused by antibiotic treatment? It seems counterintuitive to give the patient more antibiotics, but that actually has been the most common practice in the last few decades. Understandably, due to the nature of C. diff infections, up to 35% of treated cases relapse within 8 weeks post treatment (Singha et al., 2019). This shows the critical need for new or more effective treatments for CDI. </span></span></span></p> <p style="text-indent:0in"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">            In 1958, Dr. Eiseman of the United States was the first physician to show high success rates in treating colitis with what would later be known as Fecal Microbiota Transplant (FMT). This essentially involved isolating the microbiota from a healthy individual’s stool, and using it to recolonize the microbiomes of infected individuals. The good bacteria from the donor would outcompete the pathogenic bacteria in the patient’s system, reclaiming the digestive tract. However, it took 55 years before randomized controlled trials of FMT were conducted. In fact, the initial numbers showed a 90% cure rate, leading researchers to switch all patients over from antibiotic treatment to FMT before the end of the investigation (Van Nood et al., 2013) Researchers of this study, Jorup-Rönström et al.,  set out to conduct a similar FMT experiment treating 32 patients with CDI. 22 out of 32 patients were cured outright, with an additional 4 patients experiencing significantly less severity of their symptoms. This translates to over an 81% success rate in the study. With results like these, why did it take so long before adopting new strategies to combat CDI?</span></span></span></p> <p style="text-indent:0in"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">            Dr. Eiseman completed his preliminary study in 1958, during a time of great development in modern medicine. Antibiotics had just come from left field as a miracle cure in the previous decade, while the next several years were saturated with new antibiotic discovery and implementation, putting FMT on the backburner until now. Overuse of antibiotics during these years contributed towards the growing problem of multi-drug resistant organisms (Llor and Bjerrum, 2014). In fact, with C. diff in particular, the CDC has classified it as an “Urgent Threat”, its highest level classification of dangerous organisms, due to its drug resistance. Additionally, a “fecal transplant” has a fairly bad connotation and could, understandably, deter potential patients from trying the treatment. Regardless, FMT is gaining ground and is already the go-to treatment for patients with recurrent CDI. Hopefully, we will be able to see it gain further popularity in medical institutions during this era where multi-drug resistance is becoming more common.</span></span></span></p> <p style="text-indent:0in"> </p> <p style="text-indent:0in"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">Link to this article: <a href="https://doi.org/10.3109/00365521.2012.672587" style="color:#0563c1; text-decoration:underline">https://doi.org/10.3109/00365521.2012.672587</a> Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients</span></span></span></p> <p style="text-indent:0in"> </p> <p style="text-indent:0in"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">References</span></span></span></p> <p style="text-indent:0in"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">Dethlefsen, L. et al. (2008) ‘The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing’, PLoS Biology, 6(11). doi: 10.1371/journal.pgen.1000255.</span></span></span></p> <p style="text-indent:0in"> </p> <p style="text-indent:0in"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">Llor, C. and Bjerrum, L. (2014) ‘Antimicrobial resistance: Risk associated with antibiotic overuse and initiatives to reduce the problem’, Therapeutic Advances in Drug Safety, 5(6), pp. 229–241. doi: 10.1177/2042098614554919.</span></span></span></p> <p style="text-indent:0in"> </p> <p style="text-indent:0in"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">Van Nood, E. et al. (2013) ‘Duodenal infusion of donor feces for recurrent clostridium difficile’, New England Journal of Medicine, 368(5), pp. 407–415. doi: 10.1056/NEJMoa1205037.</span></span></span></p> <p style="text-indent:0in"> </p> <p style="text-indent:0in"><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">Singha, T. et al. (2019) ‘Updates in Treatment of Recurrent Clostridium difficile Infection’, Journal of Clinical Medicine Research, 11(7), pp. 465–471. doi: 10.1001/jama.2018.18993.</span></span></span></p> <p style="text-indent:0in"> </p> <p style="text-indent:0in"> </p> </div> <div class="field field--name-field-barista-posts-full-image field--type-image field--label-hidden field__item"> <img src="/lacy-lab/sites/default/files/styles/barista_posts_full_image/public/Bermudez.PNG?itok=XYmWj8SL" width="324" height="576" alt="" typeof="foaf:Image" class="image-style-barista-posts-full-image" /> </div> <div> <strong>Tags</strong> <div> <div><a href="/lacy-lab/adventure-travel-guide-microbial-world?tag=12" hreflang="und">Paper Review</a></div> </div> </div> <div class="field field--name-field-lockdown-auth field--type-string field--label-above"> <div class="field__label">Lockdown Auth</div> <div class="field__item">1</div> </div> Tue, 11 Feb 2020 14:13:27 +0000 lacydb1 258 at https://www.vumc.org/lacy-lab