Biology

Signals and Nutrient Sensing in Microbial Communities
Vanessa Sperandio, The University of Texas Southwestern Medical Center

Research in my laboratory investigates chemical, stress and nutritional signaling at the interface amongst the mammalian host, beneficial microbiota and invading pathogens. We devise a multi-disciplinary research program utilizing genetic, biochemical, chemical and structural approaches to investigate fundamental biological questions. The main tenant of research in my laboratory are the study of how bacterial cells sense several mammalian hormones as a means to gage the physiological and immune state of the host, leading to rewiring and reprogramming of bacterial transcription towards host and niche adaptation. We have also identified the first bacterial receptors to mammalian hormones, and reported that invading pathogens hijack these inter-kingdom signaling systems to promote virulence expression. We then translated these basic science concepts into strategies to develop novel approaches to anti-microbial therapy. This is a first-in-class anti-virulence approach that targets a bacterial receptor, QseC, to the host epinephrine and norepinephrine hormones that is key to activate virulence in many Gram-negative pathogens. We developed small molecule inhibitors of QseC that are effective in treating and preventing bacterially-mediated disease against several Gram-negative pathogens during mammalian infection. A key point to this therapy is that it is unlikely to lead the development of drug-resistance given that it halts bacterial virulence, but does not interfere with bacterial growth.

Background Review Article:
Curtis, Meredith M., and Vanessa Sperandio. "A complex relationship: the interaction among symbiotic microbes, invading pathogens, and their mammalian host." Mucosal immunology 4.2 (2011): 133-138.

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