Research Emphasis: Yersinia pestis is the causative agent of the plague, a highly infectious, rapidly spreading flea-borne disease that affects most mammals, including humans. It is a recently evolving pathogen, growing in its virulence and environmental stability from its most recent ancestors. The bacteria infect from a variety of routes, including through the skin via a flea bite and the inhalation of infectious aerosols, both routes of transmission that do not occur in its genetically related pathogens. These properties are the result of the ability of the bacterium to replicate to high titers in the blood whereby transmission to the flea vector and entry into the respiratory environment are enabled. Two major bacterial virulence factors, the type III secretion system and the pigmentation locus carry out immune evasion necessary for disease. Our laboratory is interested in understanding the underlying host pathogen interactions involving these virulence factors that contribute to the extreme virulence of Y. pestis, enhanced transmission to the flea vector and the worldwide persistence of the plague.