Blog RSS

New molecular imaging approach could aid vast areas of health, disease

cassatje — Wed, 04 Apr 2018 19:29:17 +0000

New molecular imaging approach could aid vast areas of health, disease cassatje Wed, 04/04/2018 - 14:29 RSS:

Matt O'Connor (Health Imaging)

http://www.healthimaging.com/topics/molecular-imaging/new-molecular-imaging-approach-could-aid-vast-areas-health-disease

A new multimodal imaging approach produced highly-advanced molecular three-dimensional (3D) images of staph infection and may be instrumental in fighting antibiotic resistant infections, according to research published online March 14 in Science Translational Medicine.

“I’m pretty convinced that these are the most advanced images in infection biology,” said corresponding author Eric Skaar, PhD, MPH, with the Department of Pathology, Microbiology and Immunology at Vanderbilt in a university news story.

Researchers used multiple types of molecular imaging to probe an invasive Staphylococcus aureus or staph infection in a mouse. The approach produced new insights into the infection that can be broadly applied to any health or disease state, Skaar said.

"We came up with this idea of putting all of these imaging modalities together to ask really exciting questions," Skaar said. "When a mouse is infected with a horrible pathogen like staph, can we see how infection damages the tissue, how metals and metalloproteins (metal-binding proteins) are affected, and how bacteria change gene expression, all in one experiment?"

The team used MRI to visualize anatomy, imaging mass spectrometry to follow protein changes, another type of mass spectrometry to study the distribution of metals and bioluminescence imaging to visualize bacterial genes that are expressed when iron is scarce.

Skaar and colleagues also determined that abscesses, the area of inflammation around a bacterial infection—long thought to be identical, actually contained different molecular environments. A finding that may aid vaccine and therapeutic development.

"We can use these imaging modalities to identify proteins that are always expressed by the bacteria, as opposed to genes that are differentially expressed depending on the environment that the bacteria experience. Those factors would be excellent drug targets," Skaar said in the report.

The imaging technique used in this study might also be useful for diagnosing an infectious agent and determining its resistance to certain antibiotics without having to culture it

Lockdown Auth

New imaging approach offers unprecedented views of staph infection

cassatje — Wed, 04 Apr 2018 19:26:29 +0000

New imaging approach offers unprecedented views of staph infection cassatje Wed, 04/04/2018 - 14:26 RSS:

EurekAlert!

https://www.eurekalert.org/pub_releases/2018-03/vumc-nia031218.php

Eric Skaar, PhD, MPH, marvels at the images on his computer screen -- 3-D molecular-level views of infection in a mouse. "I'm pretty convinced that these are the most advanced images in infection biology," said Skaar, Ernest W. Goodpasture Professor of Pathology.

Skaar and colleagues at Vanderbilt including James Cassat, MD, PhD, assistant professor of Pediatrics, combined multiple types of molecular imaging to probe an invasive Staphylococcus aureus ("staph") infection in the mouse. Their integrated imaging approach, reported this week in Science Translational Medicine, revealed new insights about staph infections and can be broadly applied to any health or disease state, Skaar said.

Antibiotic-resistant forms of staph are a leading cause of hospital-acquired infections, infectious heart disease, and pus-forming skin and soft-tissue infections.

The unique imaging resources available at Vanderbilt made the unprecedented 3-D imaging possible, Skaar said.

These resources include animal imaging technologies available through the Vanderbilt University Institute of Imaging Science, directed by John Gore, PhD, and imaging mass spectrometry technologies available through the Mass Spectrometry Research Center, directed by Richard Caprioli, PhD.

Skaar and his team are interested in the battle between host and pathogen for limited nutrients, particularly metals like iron, zinc and manganese. Identifying molecules involved in this struggle could point to novel diagnostic and therapeutic targets for infectious diseases. Over the past several years, the investigators have used various imaging modalities to study infection. Each approach has its own strengths, Skaar said. Magnetic resonance imaging (MRI), for example, shows how the physical anatomy changes in response to infection. Mass spectrometry reveals specific molecules with high sensitivity. Bioluminescence imaging (BLI) lets investigators study changes in gene expression in vivo.

The approach was successful.

The investigators used MRI to visualize anatomy, imaging mass spectrometry to follow protein changes, another type of mass spectrometry to study the distribution of metals, and BLI to visualize bacterial genes that are expressed when iron is scarce.

Their studies showed that "not all abscesses are created equal," Skaar said. Historically, abscesses -- the area of inflammation around a bacterial infection -- have been considered to be identical and simply "big bags of pus." But Skaar and his team found that abscesses, even in the same tissue, have different molecular environments. Some metals are excluded from all abscesses, and some metals are in one abscess, but not in another. Within an abscess, the metal distribution is not uniform, suggesting an underlying abscess substructure, Skaar noted.

The staph bacteria responded to this molecular heterogeneity by expressing different genes in different abscesses -- a discovery that is not possible to make using standard techniques that combine all abscesses together. The findings have implications for vaccine and therapeutic development.

The researchers also discovered that a key immune defense protein in neutrophils does not reach the bacterial cells. Looking at an image, Skaar pointed out "the immune protein made by neutrophils is a blue cloud, coming to get the bacterial microcolony," represented by a purple dot.

The two colors never meet.

"There is a demilitarized zone in between the neutrophil protein and the bacterial microcolony," Skaar said, noting that the investigators do not know what is in this zone. "Whatever staph is doing, it's excellent at keeping the immune system from getting to it."

The multi-modality imaging approach is a powerful tool for making basic science discoveries about the host-pathogen interaction, which could reveal new therapeutic targets.

Using imaging to identify bacterial proteins might also be useful for diagnosing an infectious agent -- and assessing its resistance to certain antibiotics -- without having to culture it, Skaar said. Culture-free diagnosis would require a tissue sample that is amenable to imaging mass spectrometry.

###

Cassat and postdoctoral research fellow Jessica Moore, PhD, are co-first authors of the Science Translational Medicine paper.

The research was supported by grants from the National Institutes of Health (AI132560, AI113107, AI107233, AI069233, AI101171, AI073843, GM103391), the Burroughs Wellcome Fund and the Defense Advanced Research Projects Agency. The instrumentation in the Mass Spectrometry Research Center was supported by NIH grants OD012359 and RR026742.

Skaar is professor of Pathology, Microbiology and Immunology, director of the Microbial Pathogenesis Program and director of the Institute for Infection, Immunology, and Inflammation. Gore is University Professor of Radiology and Radiological Sciences and Hertha Ramsey Cress Professor of Medicine. Caprioli is Stanford Moore Professor of Biochemistry.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Lockdown Auth

Physician-scientist is dream job for Vanderbilt’s Cassat

cassatje — Fri, 05 Dec 2014 15:42:20 +0000

Physician-scientist is dream job for Vanderbilt’s Cassat cassatje Fri, 12/05/2014 - 09:42 RSS:

Leigh MacMillan

http://news.vanderbilt.edu/2014/12/physician-scientist-cassat/

Lockdown Auth

Need For CF Patients To Avoid MRSA Underscored By New Research

cassatje — Thu, 30 Oct 2014 20:11:57 +0000

Need For CF Patients To Avoid MRSA Underscored By New Research cassatje Thu, 10/30/2014 - 15:11 RSS:

http://cysticfibrosisnewstoday.com/2014/10/20/need-for-cf-patients-to-avoid-staphylococcus-aureus-underscored-by-new-research/

Lockdown Auth

Study shows bacteria can form ‘gangs,’ resist treatment

cassatje — Tue, 28 Oct 2014 15:27:30 +0000

Study shows bacteria can form ‘gangs,’ resist treatment cassatje Tue, 10/28/2014 - 10:27 RSS:

http://www.tennessean.com/story/news/health/2014/10/26/study-shows-bacteria-can-form-gangs-resist-treatment/17930511/

Article from The Tennesseean

Lockdown Auth

STAPH BACTERIA GANG UP TO OUTSMART ANTIBIOTICS

cassatje — Tue, 21 Oct 2014 20:36:48 +0000

STAPH BACTERIA GANG UP TO OUTSMART ANTIBIOTICS cassatje Tue, 10/21/2014 - 15:36 RSS:

http://www.futurity.org/infectious-diseases-antibiotics-786212/

Lockdown Auth

Staph 'gangs' share nutrients during infection, study finds

cassatje — Fri, 17 Oct 2014 15:26:23 +0000

Staph 'gangs' share nutrients during infection, study finds cassatje Fri, 10/17/2014 - 10:26 RSS:

http://medicalxpress.com/news/2014-10-staph-gangs-nutrients-infection.html

Lockdown Auth

Staph 'gangs' share nutrients during infection

cassatje — Fri, 17 Oct 2014 15:24:36 +0000

Staph 'gangs' share nutrients during infection cassatje Fri, 10/17/2014 - 10:24 RSS:

http://www.sciencedaily.com/releases/2014/10/141016140932.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A%20sciencedaily%20%28Latest%20Science%20News%20--%20ScienceDaily%29

Lockdown Auth

Staph "gangs" share nutrients during infection: study

cassatje — Thu, 16 Oct 2014 17:35:24 +0000

Staph "gangs" share nutrients during infection: study cassatje Thu, 10/16/2014 - 12:35 RSS:

http://news.vanderbilt.edu/2014/10/staph-shares-during-infection/

Article detailing findings from the Cassat and Skaar labs.

Lockdown Auth

Cassat lands Burroughs Wellcome Fund award

cassatje — Mon, 13 Oct 2014 21:00:39 +0000

Cassat lands Burroughs Wellcome Fund award cassatje Mon, 10/13/2014 - 16:00 RSS:

http://news.vanderbilt.edu/2014/07/cassat-lands-burroughs-wellcome-fund-award/

Vanderbilt Reporter article about the Cassat Lab's receipt of a Burroughs Wellcome Fund Career Award

Lockdown Auth

Staph-killing compound may be effective against osteomyelitis

cassatje — Mon, 13 Oct 2014 20:57:39 +0000

Staph-killing compound may be effective against osteomyelitis cassatje Mon, 10/13/2014 - 15:57 RSS:

http://www.news-medical.net/news/20130620/Staph-killing-compound-may-be-effective-against-osteomyelitis.aspx

News Medical blog about Cassat and Skaar lab research

Lockdown Auth

Staph Bone Infections Have A New Model, And Possibly A New Treatment

cassatje — Mon, 13 Oct 2014 20:56:34 +0000

Staph Bone Infections Have A New Model, And Possibly A New Treatment cassatje Mon, 10/13/2014 - 15:56 RSS:

http://www.medicalnewstoday.com/releases/262282.php

Medical News Today article about the Cassat lab osteomyelitis model

Lockdown Auth

A new model -- and possible treatment -- for staph bone infections

cassatje — Mon, 13 Oct 2014 20:55:18 +0000

A new model -- and possible treatment -- for staph bone infections cassatje Mon, 10/13/2014 - 15:55 RSS:

http://www.sciencedaily.com/releases/2013/06/130619164706.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A%20sciencedaily%20%28ScienceDaily%3A%20Latest%20Science%20News%29

Science Daily article about Cassat Lab osteomyelitis research

Lockdown Auth

Osteomyelitis progress reported

cassatje — Mon, 13 Oct 2014 20:53:27 +0000

Osteomyelitis progress reported cassatje Mon, 10/13/2014 - 15:53 RSS:

http://www.hcahospitals.co.uk/blog/osteomyelitis-progress-reported/

HCA Hospitals Blog about Cassat Lab research

Lockdown Auth

NEW STAPH-KILLING COMPOUND FOR OSTEOMYELITIS

cassatje — Mon, 13 Oct 2014 20:51:51 +0000

NEW STAPH-KILLING COMPOUND FOR OSTEOMYELITIS cassatje Mon, 10/13/2014 - 15:51 RSS:

Elizabeth Hofheinz, M.P.H., M.Ed.

http://ryortho.com/breaking/new-staph-killing-compound-for-osteomyelitis/

Article in Orthopedics this Week about Cassat and Skaar Lab research

Lockdown Auth

Staphylococcus aureus Osteomyelitis: Bad to the Bone

cassatje — Mon, 13 Oct 2014 20:42:23 +0000

Staphylococcus aureus Osteomyelitis: Bad to the Bone cassatje Mon, 10/13/2014 - 15:42 RSS:

Michael Olson and Alex Horswill

http://www.sciencedirect.com/science/article/pii/S1931312813001984

Write-up of Cassat Lab publication in Cell Host and Microbe 2013

Lockdown Auth

New Staph Killer Compound For Osteomyelitis

cassatje — Mon, 13 Oct 2014 20:39:58 +0000

New Staph Killer Compound For Osteomyelitis cassatje Mon, 10/13/2014 - 15:39 RSS:

http://boneandspine.com/new-staph-killer-compound-for-osteomyelitis/

Article from Bone and Spine featuring the Cassat Lab osteomyelitis model

Lockdown Auth

Studies outline new model for staph bone infections

cassatje — Mon, 13 Oct 2014 20:37:07 +0000

Studies outline new model for staph bone infections cassatje Mon, 10/13/2014 - 15:37 RSS:

http://news.vanderbilt.edu/2013/06/staph-bone-infections/

Article on the Cassat Lab osteomyelitis model in the Vanderbilt Reporter

Lockdown Auth