Blog RSS https://www.vumc.org/lacy-lab/ en 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 The Cinnamon Challenge https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/cinnamon-challenge <span class="field field--name-title field--type-string field--label-hidden">The Cinnamon Challenge</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, 02/09/2020 - 18:18</span> <a href="/lacy-lab/blog-post-rss/257" class="feed-icon" title="Subscribe to The Cinnamon Challenge"> 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_Miriam</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; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><i>Pseudomonas aeruginosa</i> is a notorious opportunistic pathogen best known for causing lung infections in patients with cystic fibrosis and compromised immune systems. Interestingly, this pathogen has the capability of communicating with other bacteria via a phenomenon called quorum sensing. <i>P. aeruginosa </i>produces metabolites, often termed autoinducers, that accumulate during growth. When these metabolites reach a certain concentration, they trigger changes in gene expression in surrounding bacteria. These changes can lead to shifts in metabolism as well as changes in virulence potential (1). Inhibiting quorum sensing to reduce virulence and infection has been of interest to many investigators, including a group in India that has shown the inhibitory effects of cinnamon oil on biofilm formation and virulence factors that are regulated by quorum sensing (2).</span></span></span></p> <p style="text-align:justify; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">Like the spice in your kitchen cabinet, cinnamon oil is derived from the bark and leaves of the true cinnamon tree. Cinnamon oil, of which the most abundant ingredient is cinnamaldehyde, has been shown to exhibit antimicrobial properties and is of interest as an alternative to antibiotics in the wake of antibiotic resistance concerns. In this study by Kalia et al., investigators set out to determine the effects of cinnamon oil on the growth, biofilm formation, and production of virulence factors by <i>P. aeruginosa. </i>Concentrations of cinnamon oil greater than 0.2 <span style="font-family:&quot;Times New Roman&quot;,serif">µ</span>l/ml were shown to reduce the growth rate of <i>P. aeruginosa. </i>The minimum inhibitory concentration for cinnamon oil was 1 <span style="font-family:&quot;Times New Roman&quot;,serif">µ</span>l/ml, which can be compared to an MIC of 8 <span style="font-family:&quot;Times New Roman&quot;,serif">µ</span>g/ml of the antibiotic tobramycin (3).<i> </i>In addition to growth, the production of pyocyanin, an important virulence factor that generates reactive oxygen species, was reduced in the presence of ≥0.2 <span style="font-family:&quot;Times New Roman&quot;,serif">µ</span>l/ml cinnamon oil. Cinnamon oil was also shown to inhibit swarming activity of <i>P. aeruginosa</i>, which is important for colonization. The production of alginate, a component of extracellular polysaccharide important for biofilm stability, was also significantly reduced by the addition of cinnamon oil. Overall, biofilm production was shown to be reduced by 31% in the presence of 0.2 <span style="font-family:&quot;Times New Roman&quot;,serif">µ</span>l/ml cinnamon oil.</span></span></span></p> <p style="text-align:justify; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">While this study provides interesting preliminary findings on the effects of cinnamon oil, it is still unclear whether the effects are truly due to the disruption of quorum sensing or other off target effects. The arguments from this study would be more convincing by the addition of transcriptomic and proteomic data. These data would help determine if genes (and the products they encode) that are known to be regulated by quorum sensing are downregulated in the presence of cinnamon oil. In addition, a mammalian infection model in which cinnamon oil is used as a treatment would also add evidence for quorum sensing inhibition. Testing cinnamon oil in an animal model would be an important point for proving its efficacy against <i>P. aeruginosa</i>, assuming the end goal would be to market cinnamon oil as a therapeutic for human infection.</span></span></span></p> <p style="text-align:justify; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">This study is a great example of investigating natural products to be used against pathogens as an alternative to antibiotics to which bacteria can develop resistance. It is evident that cinnamon oil certainly has an inhibitory effect on the growth, biofilm formation, and production of virulence factors by <i>P. aeruginosa, </i>but further investigation is required before it can be denoted as an inhibitor of quorum sensing. And so, it may be better to take a trip to the doctor’s office instead of swallowing a spoonful of cinnamon.</span></span></span></p> <p style="text-align:justify; 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="text-align:justify"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">Rutherford ST, Bassler BL. Bacterial Quorum Sensing: its role in virulence and possibilities of its control. Cold Spring Harbor Prespect Med. 2012; 2(11): a012427.</span></span></span></li> </ol> <p style="margin-left:24px; text-align:justify"> </p> <ol start="2"> <li style="text-align:justify"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">Kalia M, Yadav VK, Singh PK, Sharma D, Pandey H, Narvi SS, et al. (2015) Effect of Cinnamon Oil on Quorum Sensing-Controlled Virulence Factors and Biofilm Formation in Pseudomonas aeruginosa. PLoS ONE 10(8): e0135495. doi:10.1371/journal.pone.0135495</span></span></span></li> </ol> <p style="margin-left:48px"> </p> <ol start="3"> <li style="text-align:justify; margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif">Ratjen F, Brockhaus F, Angyalosi G, 2009. Aminoglycoside therapy against Pseudomonas aeruginosa in cystic fibrosis: a review. J. Cyst. Fibros. 8, 361e369.</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/Miriam.png?itok=9-NXDXNR" width="449" height="539" 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> Mon, 10 Feb 2020 00:18:23 +0000 lacydb1 257 at https://www.vumc.org/lacy-lab Are viruses alive? https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/are-viruses-alive <span class="field field--name-title field--type-string field--label-hidden">Are viruses alive?</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">Fri, 02/07/2020 - 15:21</span> <a href="/lacy-lab/blog-post-rss/256" class="feed-icon" title="Subscribe to Are viruses alive?"> 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 Mansueto</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">            There has been much debate as to whether viruses constitute living organisms. In a magazine article from the Microbiology Society titled “Are Viruses Alive”, two microbiologists discussed whether viruses should be considered living organisms. Nigel Brown, the first interviewee, explains that viruses need a host cell to replicate, which goes against one of the eight characteristics of life. Additionally, Brown explains that many viruses lack ribosomes and proteins needed to sustain a proper metabolism. Contrastingly, David Bhella, the second interviewee, explains that viruses could be considered living if one defines life as the ability to evolve, not the metabolic-focused definition that other biologists use. In consideration of this definition, viruses are found to evolve rapidly which may suggest that they are indeed alive<sup>1</sup>. Though scientists are still discussing whether viruses should be considered living, a new type of virus, giant viruses, has added a quizzical new perspective on what viruses are. In 2003, a team discovered a virus named mimivirus from <i>Acanthamoeba polyphaga</i> that had a genome size of 800 kb. The overall size of the virus particle is 400 nm which rivals that of multiple species of bacteria<sup>2</sup>. These viruses have very unique gene sets when compared to other viruses and canonically known living organisms<sup>3</sup>. Additionally, these giant viruses are found to have some metabolic pathways which, to some, seem to suggest that viruses may be living organisms.</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">            In the podcast “This Week in Virology: Endless Giant Virus Forms Most Beautiful”, Alexandra Worden describes a giant virus her team unintentionally discovered. Worden and her group found a 900 kb-sized giant virus in a choanoflagellate that has 862 predicted proteins and a GC content of 22%. It was the low GC content that facilitated the isolation and ultimately the sequencing of the viral genome as the team separated the low GC fraction of DNA from the choanoflagellate’s genome. This virus was found to have three rhodopsin-like proteins in its genome. These proteins were expressed in <i>Escherichia coli</i> where it was found that all three absorb different wavelengths of light. Upon the absorption of their specific spectra of light, they can pump protons across a membrane which is suggested to facilitate the choanoflagellate they infect with carbon fixation in the form of photoheterotrophy. Additionally, the virus has the full metabolic pathway for making the pigments needed in its rhodopsin proteins. This virus may bring a new metabolic pathway for the choanoflagellate which may provide a mutualistic relationship with this protist. However, both the choanoflagellate and the virus have not been cultured. Although transgenic expression suggest these rhodopsin proteins play a role in the choanoflagellate cell, the rhodopsin proteins must be studied <i>in vivo</i> before conclusions can be drawn as to how the virus interacts with its host cell<sup>4,5</sup>.</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">            Though more work needs to be done to fully research this giant virus, Worden’s team brings a fascinating new virus-eukaryotic host interaction to light that is somewhat similar to coral and zooxanthellae. With regard to the current debate on the legitimacy of viruses being living organisms, giant viruses seem to provide examples where a virus can have a metabolism. Though the study of giant viruses does not entirely guarantee viruses may be accepted as a lifeform, they certainly bring a new perspective into sophisticated relationships with how these giant viruses interact with their host organisms. Additionally, the high diversity and uniqueness of giant viruses may provide clues towards the origins of life, information on the evolution of viruses, or new metabolic pathways never seen before.  </span></span></span></p> <ol> <li><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#333333">Society, M. (n.d.). Are viruses alive? Retrieved from </span><a href="https://microbiologysociety.org/publication/past-issues/what-is-life/article/are-viruses-alive-what-is-life.html" style="color:#0563c1; text-decoration:underline">https://microbiologysociety.org/publication/past-issues/what-is-life/article/are-viruses-alive-what-is-life.html</a></span></span></span></li> <li><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="background:white"><span style="color:#222222">La Scola, B., Audic, S., Robert, C., Jungang, L., de Lamballerie, X., Drancourt, M., ... &amp; Raoult, D. (2003). A giant virus in amoebae. <i>Science</i>, <i>299</i>(5615), 2033-2033.</span></span></span></span></span></li> <li><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#333333">Giant Viruses. (2018, February 2). Retrieved from <a href="https://www.americanscientist.org/article/giant-viruses">https://www.americanscientist.org/article/giant-viruses</a></span></span></span></span></li> <li style="margin-bottom:11px"><span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><a href="https://www.asm.org/Podcasts/TWiV/Episodes/Endless-giant-virus-forms-most-beautiful-TWiV-575" style="color:#0563c1; text-decoration:underline">https://www.asm.org/Podcasts/TWiV/Episodes/Endless-giant-virus-forms-most-beautiful-TWiV-575</a> </span></span></span></li> <li style="margin-bottom:11px"><span style="font-size:11.0pt"><span style="background:white"><span style="line-height:107%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#222222">Needham, D. M., Yoshizawa, S., Hosaka, T., Poirier, C., Choi, C. J., Hehenberger, E., ... &amp; Kurihara, R. (2019). A distinct lineage of giant viruses brings a rhodopsin photosystem to unicellular marine predators. <i>PNAS </i></span></span></span></span></span><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"><i>116</i>(41), 20574-20583.</span></span></span></span></span></li> </ol> <div> <hr align="left" class="msocomoff" size="1" width="33%" /> <div> <div class="msocomtxt" id="_com_1" language="JavaScript" onmouseout="msoCommentHide('_com_1')" onmouseover="msoCommentShow('_anchor_1','_com_1')"><a name="_msocom_1" id="_msocom_1"></a></div> </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/Mansueto.png?itok=8MblFrf4" width="289" height="289" 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> Fri, 07 Feb 2020 21:21:23 +0000 lacydb1 256 at https://www.vumc.org/lacy-lab Coronavirus Susceptibility to the Antiviral Remdesivir https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/coronavirus-susceptibility-antiviral-remdesivir <span class="field field--name-title field--type-string field--label-hidden">Coronavirus Susceptibility to the Antiviral Remdesivir</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, 02/05/2020 - 15:37</span> <a href="/lacy-lab/blog-post-rss/255" class="feed-icon" title="Subscribe to Coronavirus Susceptibility to the Antiviral Remdesivir"> 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">AlexInWonderland</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">Coronaviruses (CoVs) can cause significant disease in humans, as was evident in the severe acute respiratory syndrome (SARS) outbreak in 2002, the Middle Eastern respiratory syndrome (MERS) outbreak in 2012, and the ongoing outbreak in Central China of a yet to be genetically defined CoV (2). Currently, there are no approved therapeutics available, however, Agostini et al. details the effects of a nucleoside analogue that potently inhibits human and zoonotic CoVs <i>in vitro. </i>Remdesivir (GS-5734) acts as an inhibitor of viral replication and inhibits murine hepatitis virus (MHV), SARS-CoV, and MERS-CoV with similar 50% effective concentration values (EC<sub>50</sub>). Given the emergence potential of CoVs to cause deadly disease, novel antivirals will be critical in preventing the next epidemic.  </span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">CoVs belong to the order Nidovirales and are enveloped, non-segmented, positive sense, single-stranded RNA viruses. CoVs account for the largest identified RNA genomes, with most being approximately 30kb. Two thirds of the genome encode for the replicase-nonstructural proteins, with the remaining third encoding for the structural units: spike (S), envelope (E), membrane (M), and nucleocapsid (N) (3). Nonstructural protein 14, ExoN, mediates exoribonuclease activity and provides a level of resistance to GS-5734.  At 0.25 µM of drug, MHV ExoN knockout strain (ExoN-) exhibits a 100-fold greater reduction in viral titer when compared to wild type (WT) MHV. The EC<sub>50</sub> of ExoN- MHV was 0.019 μM, a 4.5-fold decrease compared to WT EC<sub>50</sub> of 0.087 µM.  This increased sensitivity of ExoN- MHV is suggestive of a mechanism of action for GS-5734 that involves incorporation of drug into viral RNA that can be removed by the proofreading activity of ExoN.  Additionally, the EC<sub>50</sub> for both SARS-CoV and MERS-CoV was approximately 0.074 μM for both viruses (1). </span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Following 23 passages of WT MHV in the presence of increasing concentrations of GS-441524, the parent nucleoside analogue to GS-5734, increased viral cytopathic effect (CPE) was observed, indicative of the virus’s ability to replicate.  GS-441524 and GS-5734 are metabolized in the same manner, but GS-441524 has a broader range of working concentrations and thus was used for this particular assay (6). Full genome sequencing revealed 6 non-synonymous mutations, two of which were found in the predicted fingers domain of the conserved right-hand structure of the RNA dependent RNA polymerase (F476L and V553L) (4,5).  Engineered MHV containing either mutation individually was more sensitive to GS-5734 than WT MHV, while recombinant MHV containing both mutations displayed a level of resistance similar to that of the P23 lineage.  In comparison to WT MHV, recombinant F476L MHV, V553L MHV, and F476L + V553L MHV displayed a 2.4, 5, and 5.6-fold resistance to GS-5734. However, recombinant F476L + V553L MHV could not compete with WT MHV via co-infection of murine DBT cells in the absence of GS-5734, suggesting that the increased resistance to drug comes at a fitness cost to the virus (1). </span></span></p> <p style="text-indent:.5in"><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Broadly reactive antivirals against human CoV infections, such as the recently confirmed outbreak in East Asia, are imperative in the fight to control and prevent potential epidemics. Agostini et al. provides conclusive evidence that GS-5734 is highly active against CoVs and that resistant viruses endure a loss of competitive fitness <i>in vitro</i>. The pro-drug Remdesivir, GS-5734, has proved to be a promising contender in the family of small molecule, nucleoside analogue drugs.  </span></span></p> <p style="text-indent:.5in"> </p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Resources:</span></span></p> <ol> <li><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Agostini, M. L., Andres, E. L., Sims, A. C., Graham, R. L., Sheahan, T. P., Lu, X., Smith, E. C., Case, J. B., Feng, J. Y., Jordan, R., Ray, A. S., Cihlar, T., Siegel, D., Mackman, R. L., Clarke, M. O., Baric, R. S., &amp; Denison, M. R. (2018). Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio, 9(2), e00221-18, /mbio/9/2/mBio.00221-18.atom. <a href="https://doi.org/10.1128/mBio.00221-18" style="color:#0563c1; text-decoration:underline">https://doi.org/10.1128/mBio.00221-18</a></span></span></li> <li><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Coronavirus | home | cdc. (2020, January 16). <a href="https://www.cdc.gov/coronavirus/index.html">https://www.cdc.gov/coronavirus/index.html</a></span></span></li> <li><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Fehr, A. R., &amp; Perlman, S. (2015). Coronaviruses: An overview of their replication and pathogenesis. In H. J. Maier, E. Bickerton, &amp; P. Britton (Eds.), Coronaviruses (Vol. 1282, pp. 1–23). Springer New York. <a href="https://doi.org/10.1007/978-1-4939-2438-7_1" style="color:#0563c1; text-decoration:underline">https://doi.org/10.1007/978-1-4939-2438-7_1</a></span></span></li> <li><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Sexton, N. R., Smith, E. C., Blanc, H., Vignuzzi, M., Peersen, O. B., &amp; Denison, M. R. (2016). Homology-based identification of a mutation in the coronavirus rna-dependent rna polymerase that confers resistance to multiple mutagens. Journal of Virology, 90(16), 7415–7428. <a href="https://doi.org/10.1128/JVI.00080-16" style="color:#0563c1; text-decoration:underline">https://doi.org/10.1128/JVI.00080-16</a></span></span></li> <li><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Xu, X. (2003). Molecular model of SARS coronavirus polymerase: Implications for biochemical functions and drug design. Nucleic Acids Research, 31(24), 7117–7130. <a href="https://doi.org/10.1093/nar/gkg916" style="color:#0563c1; text-decoration:underline">https://doi.org/10.1093/nar/gkg916</a> </span></span></li> <li><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, Siegel D, Perron M, Bannister R, Hui HC, Larson N, Strickley R, Wells J, Stuthman KS, Van Tongeren SA, Garza NL, Donnelly G, Shurtleff AC, Retterer CJ, Gharaibeh D, Zamani R, Kenny T, Eaton BP, Grimes E, Welch LS, Gomba L, Wilhelmsen CL, Nichols DK, Nuss JE, Nagle ER, Kugelman JR, Palacios G, Doerffler E, Neville S, Carra E, Clarke MO, Zhang L, Lew W, Ross B, Wang Q, Chun K, Wolfe L, Babusis D, Park Y, Stray KM, Trancheva I, Feng JY, Barauskas O, Xu Y, Wong P, Braun MR, Flint M, McMullan LK, Chen S-S, Fearns R, Swaminathan S, Mayers DL, Spiropoulou CF, Lee WA, Nichol ST, Cihlar T, Bavari S. 2016. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 531:381–385. <a href="https://doi.org/10.1038/nature17180" style="color:#0563c1; text-decoration:underline">https://doi.org/10.1038/nature17180</a> </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/Alex.png?itok=ExCy-9NY" width="337" height="449" 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, 05 Feb 2020 21:37:04 +0000 lacydb1 255 at https://www.vumc.org/lacy-lab TWIM: Exosomes in your nose and in your gut https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/twim-exosomes-your-nose-and-your-gut <span class="field field--name-title field--type-string field--label-hidden">TWIM: Exosomes in your nose and in your gut</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, 02/03/2020 - 19:50</span> <a href="/lacy-lab/blog-post-rss/254" class="feed-icon" title="Subscribe to TWIM: Exosomes in your nose and in your gut"> 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">microbe_mc</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">In the podcast “Exosomes in your nose and in your gut” in the series “This Week in Microbiology”, hosts Michael Schmidt, Michele Swanson, and Vincent Racaniello talk primarily about two recent articles (Schmidt et al., 2019). The first article focuses on the immune response in nasal epithelial cells to invading pathogens. Titled “Exosome swarms eliminate airway pathogens and provide passive epithelial immunoprotection through nitric oxide”, the article describes an experiment in which nasal mucosa–derived exosomes demonstrate antimicrobial activity (Nocera et al., 2019). The study demonstrated that upon LPS activation of Toll-like receptor 4 (which occurs naturally when recognizing patterns on pathogens such as <i>Pseudomonas</i>), billions of exosomes flood the nasal passages in humans (Nocera et al., 2019). These exosomes contain nitric oxide, nitric oxide synthase, and antimicrobial peptides that combat pseudomonal bacteria effectively (Nocera et al., 2019). Additionally, after release of these exosomes following LPS stimulation, the exosomes are moved backwards through mucociliary flow into the sinuses. The podcast hosts highlight that this activates the innate immune response of “naïve cells” that have not yet encountered the invading bacteria (Nocera et al., 2019). The podcast hosts also concisely explain how this study shows a combination of the innate and adaptive immune system, and how this is a fascinating method of effectively combating airborne pathogens in the nose. </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">            Next, the podcast takes a different turn as the hosts explain how exosomes can help certain bacteria in the gut protect against inflammation in mice and humans. After describing how exosomes are multi-vesicular cells that carry cargo through budding off of host cells, the hosts look at another microbiology article titled “Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota” by Teng et al. (2018). This article is focused on exosomes in plant materials and their effect on gut microbiota composition and activity. Although the article is long and extremely detailed, the hosts summarize the key points in the podcast. Ginger exosomes, as well as other plant-derived exosomes such as carrot, garlic, turmeric and grapefruit, are introduced into either mice or humans in trials, and the results on gut microbiota observed (Teng et al., 2019). These exosomes are seen to be incorporated into and change the community composition of the gut microbiome, most likely through microRNAs contained in the exosomes (Teng et al., 2019). The lipid composition of the exosomes also determines their destination, such as the intestine or the gut (Teng et al., 2018). Additionally, ginger exosomes protect against DDS induced colitis in mice, but not in germ-free mice, indicating that these exosomes reduce inflammation through gut microbiota and not through another method (Teng et al., 2018). A proposed mechanism for this in the paper is through IL-2, a cytokine which “tightens” the gut lining so that more interior cells are protected (Schmidt et al., 2019). The ginger exosomes are shown to increase production of this cytokine (Teng et al., 2018). The paper thoroughly goes through many experiments to examine the effect of plant exosomes on gut microbiota, with 25 authors and contributions from several labs. Plant exosomes having a positive effect on gut bacteria is a novel way of vegetables benefiting gut health, and the hosts emphasized how much exciting research can be done with this in mind (Schmidt et al., 2019). </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">            The hosts did a great job at appealing to both more experienced people in the field and new students. The podcast had a good mix of scientific details and explanations as well as more personal background and information on exosomes. Although there was some content obviously geared towards more consistent viewers, such as chatting about the weather, the podcast was helpful for learning about microbes for a relative beginner such as myself. I look forward to learning more about microbes through This Week in Microbiology. </span></span></span></p> <p> </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">Schmidt, M., Swanson, M., &amp; Racaniello, V. (2019). <i>Exosomes in your nose and in your gut</i> (No. 190). </span><a href="https://www.asm.org/Podcasts/TWiM/Episodes/Exosomes-in-your-nose-and-in-your-gut-TWiM-190" style="color:#0563c1; text-decoration:underline"><span style="font-family:&quot;Times New Roman&quot;,serif">https://www.asm.org/Podcasts/TWiM/Episodes/Exosomes-in-your-nose-and-in-your-gut-TWiM-190</span></a></span></span></p> <p> </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">Teng, Y., Ren, Y., Sayed, M., Hu, X., Lei, C., Kumar, A., Hutchins, E., Mu, J., Deng, Z., Luo, C., Sundaram, K., Sriwastva, M. K., Zhang, L., Hsieh, M., Reiman, R., Haribabu, B., Yan, J., Jala, V. R., Miller, D. M., … Zhang, H.-G. (2018). Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota. <i>Cell Host &amp; Microbe</i>, <i>24</i>(5), 637-652.e8. </span><a href="https://doi.org/10.1016/j.chom.2018.10.001" style="color:#0563c1; text-decoration:underline"><span style="font-family:&quot;Times New Roman&quot;,serif">https://doi.org/10.1016/j.chom.2018.10.001</span></a></span></span></p> <p> </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">Nocera, A. L., Mueller, S. K., Stephan, J. R., Hing, L., Seifert, P., Han, X., Lin, D. T., Amiji, M. M., Libermann, T., &amp; Bleier, B. S. (2019). Exosome swarms eliminate airway pathogens and provide passive epithelial immunoprotection through nitric oxide. <i>Journal of Allergy and Clinical Immunology</i>, <i>143</i>(4), 1525-1535.e1. </span><a href="https://doi.org/10.1016/j.jaci.2018.08.046" style="color:#0563c1; text-decoration:underline"><span style="font-family:&quot;Times New Roman&quot;,serif">https://doi.org/10.1016/j.jaci.2018.08.046</span></a></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/Harrison.png?itok=2PIIkttw" width="322" 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> Tue, 04 Feb 2020 01:50:44 +0000 lacydb1 254 at https://www.vumc.org/lacy-lab Syphilis Through the Ages: Diagnostic Advancements in Detecting Treponema pallidum https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/syphilis-through-ages-diagnostic-advancements-detecting <span class="field field--name-title field--type-string field--label-hidden">Syphilis Through the Ages: Diagnostic Advancements in Detecting Treponema pallidum</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, 02/02/2020 - 18:04</span> <a href="/lacy-lab/blog-post-rss/253" class="feed-icon" title="Subscribe to Syphilis Through the Ages: Diagnostic Advancements in Detecting Treponema pallidum"> 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">Natalie F</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: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">Syphilis is a bacterial infection caused by the agent <i>Treponema pallidum </i>that can result in a variety of symptoms and progressive complications if left untreated.<i> </i>Due to the fact that the symptoms of syphilis can be mistakenly attributed to a number of other diseases, it has been named “the great masquerader” (1). Sir William Osler, a pioneering physician of the 19<sup>th</sup> and 20<sup>th</sup> century, claimed that the later stage of syphilis could produce symptoms to simulate “almost every disease known to man” (2). It was especially important to develop diagnostic tools besides clinical assessments in order to definitively identify syphilis as the disease and prescribe the appropriate treatment. The blog post “A Brief History of Laboratory Diagnostics for Syphilis”, a post by Peera Hemarajata on the American Society for Microbiology blog, succinctly illuminates the challenges and innovations in the pursuit of this diagnostic tool (3). </span></span></span></span></p> <p 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">Although syphilis as a disease has been characterized for 500 years, it wasn’t until the 20<sup>th</sup> century that the bacterial agent was observed and identified in diseased tissues by zoologist Fritz Schaudinn and dermatologist Erich Hoffman. This technique of observing <i>T. pallidum </i>in tissue was improved by the use of dark field microscopy, and high numbers of treponemes could be seen in tissue specimens. However, there were many limitations to this technique, including the fact that treponemes can only be seen in high numbers earlier in the infection and that they can only be specifically identified from certain tissues with careful preparation. For these reasons, dark field microscopy is no longer used as a diagnostic tool for syphilis (3).</span></span></span></span></p> <p 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">After microscopic observation of treponemes, there was a shift to serological testing for confirmation of syphilis. At first, these tests were non-treponemal, as they were not <i>T. pallidum </i>specific. The test was simple: if the sera of patients contained certain antibodies, first called Wasserman antibodies and then “reagins”, immune complexes would form and complement factors would be depleted, leaving erythrocytes intact which could be seen by observing the red blood cells. However, it was later determined that the antibodies were anti-phospholipid, present in response to any tissue damage and not treponemal specific. Therefore, this test yielded many false positive results. Much later, in the 1940s, it was discovered that the antigen that had prompted production of the anti-phospholipid antibodies was a diphosphatidylglycerol called cardiolipin. Why would this cardiolipin be associated with the presence of <i>T. pallidum</i>, to the extent that antibodies to this molecule could be used as a diagnostic tool? This mystery baffled researchers until only very recently, when a study in 2018 showed that <i>T. pallidum </i>produced a cardiolipin with weak immunogenicity, and furthermore, that infection of this bacteria stimulated production of cardiolipin by the host. Therefore, although this serological diagnostic test was imperfect and not treponemal specific, it was somewhat successful as a clinical tool, and also led to the development of many more non-treponemal serological diagnostic tests, some of which are still used today (3).</span></span></span></span></p> <p style="text-indent:.25in"><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">There have been further advancements in the field, owing to the identification of <i>T. pallidum </i>as the causal agent, that allow for treponemal-specific diagnostic tests. Among these are enzyme immunoassays (EIA) and chemiluminescence assays (CIA) that detect treponemal-specific antibodies, which can be automated for high-throughput screening. Looking back at the history of diagnostic tests for syphilis, the field has significantly advanced, improving the chance of early diagnosis and treatment. When I worked at a multiple sclerosis research center, one of the projects I worked on involved identifying biomarkers for cognitive dysfunction in MS patients. It can be difficult to determine which patients will develop these symptoms, which will progress and become more difficult to treat. Although multiple sclerosis and syphilis are very different diseases, I found it interesting that effective diagnostic tools are necessary for both in order to improve patient outcomes.</span></span></span></span></p> <p> </p> <ol> <li><span style="font-size:11pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span lang="ES-US" style="font-size:12.0pt" xml:lang="ES-US"><span style="font-family:&quot;Times New Roman&quot;,serif">Gonzalez-Martinez, A., et al. (2020). "Diagnosis of Syphilitic Bilateral Papillitis Mimicking Papilloedema." </span></span><u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif">Emerging Infectious Diseases</span></span></u><span style="font-size:12.0pt"><span style="font-family:&quot;Times New Roman&quot;,serif"> <b>26</b>(1): 171-173.</span></span></span></span></li> <li><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">Hemarajata, Peera. “Revisiting the Great Imitator, Part I: The Origin and History of Syphilis.” <i>ASM.org</i>, 17 June 2019, asm.org/Articles/2019/June/Revisiting-the-Great-Imitator,-Part-I-The-Origin-a?_ga=2.108552842.902210486.1578510385-1722949983.1578510385.</span></span></span></span></li> <li><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">Hemarajata, Peera. “A Brief History of Laboratory Diagnostics for Syphilis.” </span></span></span></span><i><span lang="NL" style="font-size:12.0pt" xml:lang="NL"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">ASM.org</span></span></span></span></i><span lang="NL" style="font-size:12.0pt" xml:lang="NL"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">, 6 Jan. 2020, </span></span></span></span><a href="https://www.vumc.org/lacy-lab/%20%20%20%20www.asm.org/Articles/2020/January/A-Brief-History-of-Laboratory-Diagnostics-for-Syph."><span lang="NL" style="font-size:12.0pt" xml:lang="NL"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black"><span style="text-decoration:none"><span style="text-underline:none">www.asm.org/Articles/2020/January/A-Brief-History-of-Laboratory-Diagnostics-for-Syph</span></span></span></span></span></span></a><a href="https://www.vumc.org/lacy-lab/%20%20%20%20www.asm.org/Articles/2020/January/A-Brief-History-of-Laboratory-Diagnostics-for-Syph."><span lang="NL" style="font-size:12.0pt" xml:lang="NL"><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">.</span></span></span></span></a></span></span></li> </ol> <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/Natalie.png?itok=LE7HYSb8" width="93" height="158" 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> Mon, 03 Feb 2020 00:04:10 +0000 lacydb1 253 at https://www.vumc.org/lacy-lab Are you harboring dangerous fugitives in your nose? https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/are-you-harboring-dangerous-fugitives-your-nose <span class="field field--name-title field--type-string field--label-hidden">Are you harboring dangerous fugitives in your nose? </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, 01/25/2020 - 09:47</span> <a href="/lacy-lab/blog-post-rss/252" class="feed-icon" title="Subscribe to Are you harboring dangerous fugitives in your nose? "> 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">MycobacteriumMandy</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">            Anyone that occasionally glances at the news looking for a newfound faith in humanity or has even a remote interest in the microbial world has heard of MRSA. MRSA is short for methicillin-resistant <i>Staphylococcus aureus</i>, which means these particular, pathogenic bacteria are doing their part to increase the growing worldwide problem of antibiotic-resistance! In fact, the problem of antibiotic resistance is so menacing and concerning, that in November of 2015, the World Health Organization (WHO) started a World Antibiotic Awareness Week to educate the public. With incorrect antibiotic use and increasing numbers of resistant strains, the time will come when antibiotics become completely ineffective against any sort of bacterial infection. We are progressing toward an era where if any infection is not self-limiting, no matter how minor, it can lead to sepsis and ultimately death. In the United States alone, 5-10% of people are colonized by MRSA, and 20,000 people a year die from the infection (Pettengill). The prevalence of this life-threatening organism makes it everyone’s problem. Wouldn’t it be nice if there was a way to know if you had MRSA colonizing your nares (nose holes) before it costs you hundreds of dollars in hospital bills or potentially even your life? Well, clinicians are working to do just that, and a kind blog writer from ASM (American Society for Microbiology), Matthew Pettengill has kindly broken it down for us. </span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">            The way to screen for MRSA (or any kind of <i>Staphylococcus aureus</i> colonization) is to swab the inside of an individual’s nose, but you can also swab multiple anatomical sites in order to improve the sensitivity. If an individual is hospitalized and/or immunocompromised, it seems important to recognize the presence of MRSA to prevent complications or more serious infections. The controversy comes from how exactly these swabs are tested, once they are collected. You could opt for a traditional culture method which requires using selective medias in which either MRSA or MSSA (methicillin-susceptible <i>S. aureus</i>) can be detected. There is also the molecular approach to detection which would require some sort of nucleic acid amplification-based testing, such as PCR. Many labs will perform a culture test to verify their molecular test results, allowing you to verify the presence of the potential pathogen, using two techniques.  The ability to reliably test for these bacteria is essential, however both methods have their advantages and disadvantages.</span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">            Testing for MRSA seems to be a win-win situation, but as with most things in life, there are some pros and cons associated with the different methods of screening for this extremely dangerous pathogen. The culture method of detection is not terribly sensitive, and while some studies have shown there are ways to improve this method, the improvements would make the process more labor intensive, expensive, and slow (Wolk). The molecular method of testing can improve sensitivity, but the tests can cost anywhere from $45 per test for single specimen random access assays or $20-30 per test for batch tests which are run twice a day. While there are ways to slightly cut the costs of moleculer testing, traditional culture-based testing is only $1-3 per test. Clinical labs can also run significantly more tests in a smaller period of time (Pettengill).  </span></span></p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">            Everyone can agree that MRSA is a huge burden on the healthcare system. While many strides have been made to detect the presence of these bacteria, healthcare providers still have to choose between cost-efficiency, sensitivity, and speed. More research needs to be done to perfect a detection method that would allow MRSA-testing to become a common practice.</span></span></p> <p> </p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">References:</span></span></p> <p style="text-indent:-16.55pt"><span style="font-size:12pt"><span style="background:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"> <span style="color:#333333">       Antibiotic resistance. (n.d.). Retrieved January 6, 2020, from <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance</a>.</span></span></span></span></p> <p style="text-indent:-16.55pt"><span style="font-size:12pt"><span style="background:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#333333">        Pettengill, M. (2019, July 23). Retrieved from <a href="https://www.asm.org/Articles/2019/July/MRSA-Screening-You-or-Someone-You-Love-has-MRSA-in">https://www.asm.org/Articles/2019/July/MRSA-Screening-You-or-Someone-You-Love-has-MRSA-in</a></span></span></span></span></p> <p style="text-indent:-16.55pt"><span style="font-size:12pt"><span style="background:white"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:#333333">        Wolk, D. M., Marx, J. L., Dominguez, L., Driscoll, D., &amp; Schifman, R. B. (2009). Comparison of MRSASelect Agar, CHROMagar Methicillin-Resistant Staphylococcus aureus (MRSA) Medium, and Xpert MRSA PCR    for Detection of MRSA in Nares: Diagnostic Accuracy for Surveillance Samples with Various Bacterial Densities. <i>Journal of Clinical Microbiology</i>, <i>47</i>(12), 3933–3936. doi: 10.1128/jcm.00601-09</span></span></span></span></p> <p> </p> <p><span style="font-size:12pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">            </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/Mandy.png?itok=EnOd0Xra" width="279" height="200" 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> Sat, 25 Jan 2020 15:47:51 +0000 lacydb1 252 at https://www.vumc.org/lacy-lab ASM MicroTalk: TB or not TB? That is the question…for Bill Jacobs https://www.vumc.org/lacy-lab/adventure-travel-guide-microbial-world/asm-microtalk-tb-or-not-tb-questionfor-bill-jacobs <span class="field field--name-title field--type-string field--label-hidden">ASM MicroTalk: TB or not TB? That is the question…for Bill Jacobs </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, 01/25/2020 - 09:37</span> <a href="/lacy-lab/blog-post-rss/251" class="feed-icon" title="Subscribe to ASM MicroTalk: TB or not TB? That is the question…for Bill Jacobs "> 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">Microscopic Matt Money</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;Times New Roman&quot;,serif">            Bacteria are often viewed in a negative manner as disease causing agents that are not kind to a human host.  <i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) is the epitome of a “bad bug” that can be detrimental to human health. On <a href="https://www.asm.org/Podcasts/microTalk/Episodes/TB-or-not-TB-That-is-the-Question-for-Bill-Jacobs">ASM microTalk</a>, Karl Klose discussed the history of disease, antibiotic treatment, and <i>M. tb </i>pathophysiology with<i> </i>Bill Jacobs from the Albert Einstein College of Medicine.<i> M. tb</i> is the pathogenic bacterium responsible for causing the deadly disease tuberculosis (TB). Even with a vaccine available, TB is the leading cause of death from an infectious agent worldwide, with a staggering 1.5 million deaths from TB in 2018<sup>1</sup>. TB is particularly problematic and deadly in low-income countries due to their healthcare programs not providing adequate coverage to obtain effective antibiotics to treat the disease. Antibiotic treatment of TB is fairly challenging, where patients typically take a combination of antibiotics for an extended period of time. </span></span></span></p> <p><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">            One of the main reasons that antibiotic treatment of TB is challenging is because <i>M. tb </i>grows at a slow rate. Interestingly, <i>M. tb </i>has a doubling time of 24 hours under the correct conditions, which is much longer than rapidly dividing cells like <i>E. coli</i> that have a doubling time of only 20 minutes<sup>2</sup>. Since most antibiotics target active processes that occur in dividing cells like cell wall synthesis, slow division is an advantageous mechanism by which <i>M. tb </i>avoids antibiotic killing. An extended period of time will be needed for antibiotics to be effective due to this slow growth, and this is the reason why treatment courses for TB are spanned over several months. An additional explanation for why TB is difficult to treat with antibiotics relates to mycolic acids that are found within <i>M. tb</i>’s cell wall. Mycolic acids contain up to 70-90 carbon atoms, making them extremely hydrophobic<sup>3</sup>. This hydrophobic outer barrier prevents the uptake of hydrophilic antibiotics, limiting the repertoire of antibiotics that can be used for treatment to small hydrophilic molecules like rifampicin that can pass through the barrier.</span></span></span></p> <p><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">            The mechanism by which <i>M. tb </i>is able to persist and survive within the host for an extensive period of time is by surviving the host immune response. In addition to conferring protection against antibiotics, a complex cell wall structure helps <i>M. tb </i>avoid the host immune response<sup>4</sup>. Specifically, during infection, <i>M. tb </i>infects macrophages that normally function to clear pathogens from the body. <i>M. tb </i>is essentially able to hideout and persist within macrophages by preventing intracellular degradation and macrophage apoptosis<sup>5</sup>. <i>M. tb </i>is capable of surviving in a dormant state until certain conditions within the host arise that result in symptoms and an active infection. This dormant state of <i>M. tb</i> is referred to as a latent state, where the only way that <i>M. tb</i> infection can be detected is through a skin or blood test. <i>M. tb</i>’s ability to persist in a latent state without the host showing symptoms of infection, while also being able to cause a deadly infection in some instances, exemplifies that <i>M. tb </i>is at the forefront of fascinating pathogens. </span></span></span></p> <p><span style="font-size:12pt"><span style="line-height:200%"><span style="font-family:&quot;Times New Roman&quot;,serif">  </span></span></span></p> <p align="center" style="text-align:center"><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> <ol> <li><span style="font-size:12pt"><span style="background:white"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">WORLD HEALTH ORGANIZATION. (2019). <i>Global Tuberculosis Report 2019</i>. S.l.:    </span></span></span></span></span></span></li> <li><span style="font-size:12pt"><span style="background:white"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Musuka, S., Srivastava, S., Dona, C. W. S., Meek, C., Leff, R., Pasipanodya, J., &amp; Gumbo, T.  (2013). Thioridazine Pharmacokinetic-Pharmacodynamic Parameters “Wobble” during Treatment of Tuberculosis: a Theoretical Basis for Shorter-Duration Curative Monotherapy with Congeners. <i>Antimicrobial Agents and Chemotherapy</i>, <i>57</i>(12), 5870      5877. doi: 10.1128/aac.00829-13</span></span></span></span></span></span></li> <li><span style="font-size:12pt"><span style="background:white"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Lambert, P. (2002). Cellular impermeability and uptake of biocides and antibiotics in Gram positive bacteria and mycobacteria. <i>Journal of Applied Microbiology</i>, <i>92</i>(s1). doi:    10.1046/j.1365-2672.92.5s1.7.x</span></span></span></span></span></span></li> <li><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:&quot;Times New Roman&quot;,serif"><span style="color:black">Rohini, K., &amp; Srikumar, P. S. (2013). Insights from the docking and molecular dynamics simulation of the Phosphopantetheinyl transferase (PptT) structural model from Mycobacterium tuberculosis. </span></span></span><i><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Bioinformation</span></span></i><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">, </span></span></span><i><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">9</span></span></i><span style="background:white"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">(13), 685–689. doi: 10.6026/97320630009685</span></span></span></span></span></span></li> <li><span style="font-size:12pt"><span style="background:white"><span style="line-height:200%"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="color:black">Zhai, W., Wu, F., Zhang, Y., Fu, Y., &amp; Liu, Z. (2019). The Immune Escape Mechanisms of  Mycobacterium Tuberculosis. <i>International Journal of Molecular Sciences</i>, <i>20</i>(340), 1    18. doi: doi:10.3390/ijms20020340</span></span></span></span></span></span></li> </ol> <p style="margin-left:2px"> </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/Munnecke.png?itok=KzGSw3F6" width="172" height="260" 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> Sat, 25 Jan 2020 15:37:35 +0000 lacydb1 251 at https://www.vumc.org/lacy-lab