About This ProjectStaphylococcus aureus is a highly successful human pathogen that causes approximately 800,000 life-threatening illnesses in the U.S. annually. S. aureus secretes a class of toxins known as superantigens that induce systemic and localized inflammation. We will examine the role of these proteins in the development of cardiovascular disease and type 2 diabetes.
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What is the context of this research?
Research into the microbiome has uncovered that the bacteria that colonize our bodies can have profound effects on various processes vital to our well being. Disrupting the native microbial ecology of our bodies can lead to disease. Studies indicate up to 50% of the human population is colonized with Staphylococcus aureus at any given time. Human skin and mucosal surfaces are the most common areas of colonization. This organism produces a unique class of toxins known as superantigens that interact with the immune system to cause localized and systemic inflammation. Cardiovascular disease and type 2 diabetes are characterized by systemic inflammation. The role of the S. aureus superantigens in the development of type 2 diabetes and cardiovascular disease has not been fully explored.
What is the significance of this project?
Bacterial infections that lead to disease have been thought of as an acute state of disrupted homeostasis that can be resolved by treatment with antibiotics. Research involving the microbiome indicates that some chronic diseases may be the result of byproducts of long term infection. S. aureus can colonize individuals without leading to illness and those suffering from type 2 diabetes or develop cardiovascular disease are often very heavily colonized. The superantigens produced by S. aureus are known to act systemically inducing a state of acute inflammation but their role in chronic inflammation observed in type 2 diabetes and cardiovascular disease is unknown. Information about the role of these proteins in chronic disease could lead to treatments such as vaccines and targeted therapies.
What are the goals of the project?
The primary goal of this project is to determine if superantigens have the ability to cause cardiovascular disease and type 2 diabetes through induction of systemic inflammation. Inflammation induced by these proteins will be measured by:
1. Tissue culture using aortic endothelial cells to identify if they have direct interactions that cause cell damage or disruption.
2. Measuring the uptake and clearance of glucose from adipocytes isolated from toxin treated model systems.
3. Characterizing systemic inflammation induced by superantigens using established immunological markers.
4. Identifying compounds that can be used to decrease of eliminate inflammation caused by superantigen exposure. These findings will provide a basis for further study of the role of superantigens in chronic disease.
Studying chronic illness from the standpoint of bacterial toxins is very novel. Studies challenging established dogma are intrinsically difficult to get funded and these studies could not be performed without this funding. This funding will generate data to determine if these proteins have the ability to induce the development of type 2 diabetes and cardiovascular disease. The results will also be used as preliminary data to apply for a large grant to further examine the role of these proteins in chronic disease. The funding provided for this research could fundamentally change the way we view diseases such as cardiovascular disease and type 2 diabetes, which could lead to more efficient treatments and therapies.
Meet the Team
Team BioI am currently a Microbiology Ph.D. candidate at the University of Iowa in the lab of Dr. Patrick Schlievert studying how S. aureus uses its many virulence factors to cause disease. I have always been interested in the molecular basis of disease development and how specific molecules are involved in host-pathogen interaction. My favorite part of research is the engineering aspect. I enjoy using synthetic biology to build tools and systems to examine the role of different virulence factors in disease development.
Nothing posted yet.
Press and MediaVu BG, Stach CS, Salgado-Pabón W, Diekema DJ, Gardner SE, Schlievert PM. “Superantigens of Staphylococcus aureus from Patients with Diabetic Foot Ulcers.” The Journal of infectious diseases. 2014
Paper characterizing the prevalence of S. aureus in diabetic patients and the the presence of superantigens in these isolates.
Salgado-Pabón W, Breshears L, Spaulding AR, Merriman JA, Stach CS, Horswill AR, Peterson ML, Schlievert PM. “Superantigens are critical for Staphylococcus aureus Infective endocarditis, sepsis, and acute kidney injury.” mBio. 2013
Paper indicating the important role superantigens may play in development of cardiovascular disease.
- Story on local ABC affiliate about our research:Medical Breakthrough Discovered at the Univ. of Iowa Could Save Thousands of LivesRead more at http://www.kcrg.com/news/local/Medical-Breakthroug...
- Podcast on "This week in microbiology" about superantigens and their role in disease: http://www.microbeworld.org/podcasts/this-week-in-...
- Story in IOWA NOW about our research: http://now.uiowa.edu/2013/08/bacterial-toxins-caus...
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