Our research focuses on understanding host-microbe interactions, specifically as related to plague pathogenesis. Yersinia pestis, the causative agent of plague, is a naturally occuring infection of some rodent populations. It is typically spread from rodent to rodent by their fleas. Humans may become an accidental host if they come into close contact with these infected animals or their fleas. Y. pestis has evolved to survive within each of these hosts (mammals and fleas) using a variety of virulence factors, all of which must be coordinated in response the host environment.
Photo taken by Andrew Houppert on the JOEL 1010 transmission electron microscope at the IMBI. The image shows a type III secretion needle on the surface of Y. pestis.
One of the best-studied virulence tools is the type III secretion system, which is effectively a molecular syringe that allows the bacterium to inject cytotoxic proteins (known as Yops) directly into the cytoplasm of target host cells. Type III secretion is essential for virulence in mammals, and Y. pestis mutants lacking a functional type III secretion system are avirulent. Moreover, type III secretion is a conserved tool used by numerous Gram-negative bacteria during pathogenic or symbiotic interactions with a eukaryotic host. Our research is therefore aimed at understanding the molecular mechanisms that promote type III secretion and regulate this pathway during host colonization.