Wilmara Salgado Pabón
Credentials: PhD
Position title: Assistant Professor
Email: wsalgado@wisc.edu
Address:
2015 Linden Dr. #4370
Madison, WI 53706
- Office
- 4370 Department of Pathobiological Sciences
Education
PhD Microbiology, UW-Madison
Research Summary
Infective endocarditis; Staphylococcus aureus β-Toxin
Research Detail
The pathogenesis of Staphylococcus aureus with an emphasis on the contribution of enterotoxins and cytolysins to the pathophysiology of sever disease, including sepsis, pneumonia, and infective endocarditis is the primary research focus. The long-term goal of this research program is to dissect the S. aureus mechanisms leading to these life-threatening illnesses at the molecular, cellular and whole system level.
S. aureus enterotoxins are major virulence factors in human and animal isolates. Superantigenicity (a hallmark feature of S. aureus enterotoxins) results in a T cell dependent cytokine storm leading to inflammatory syndromes. Non-hematopoietic cell interactions of enterotoxins are not well-known and poorly characterized, yet our evidence suggests that it significantly contributes to pathogenesis. A central question is then, how do these biological properties drive IE development and progression? We are currently addressing this central question utilizing isogenic infective endocarditis deficient strains complemented to produce toxoids deficient in specific function. Studies in rabbit models of pneumonia will follow. We are also characterizing the non-hematopoietic interaction of enterotoxins in in vitro systems to be followed by testing in disease models.
Endothelial cells lining the vasculature are exposed to a great variety of bloodborne stimuli and are in fact one of the first cell types to detect and respond to these stimuli, including circulating pathogens and their toxins. Pathological changes to the endothelium can result in dysregulated innate immune system activation and defects in wound healing. We are performing RNAseq analysis of endothelial cells treated with enterotoxins or cytolysins to gain a broader sense of pathways activated or manipulated by these toxins. We will also use the rabbit aortic explant culture model and rabbit models of toxemia and bacteremia to elucidate mechanisms ex vivo and in vivo. At the end, we would have defined endothelial cell functions targeted by specific S. aureus toxins and potential mechanism contributing to tissue injury. In turn, we will be able to address whether disease outcomes can be improved by intervention strategies targeting the endothelium.