Molecular Pathogenesis of Yersinia pestis.

Yersinia pestis, the etiologic agent of plague, is a gram-negative facultative intracellular bacteria of the family Enterbacteriaceae. Yersinia has a long history of precipitating massive human pandemics (e.g., the Black Death of the Middle Ages) and is still responsible for outbreaks of human disease in endemic regions of Asia, Africa, South America, and North America. Following contact with a eukaryotic cell, Yersinia exports and translocates a distinct set of virulence proteins called Yops from the cytoplasm of the bacteria into the cytoplasm of the eukaryotic cell. Once translocated into the eukaryotic cell, Yop proteins disrupt intracellular signaling pathways, prevent specific cytoskeletal rearragnements, and induce apoptotic events in macrophages. This capability enables the Yersinia to aviod phagocytosis and ensures survival of the bacteria within host tissues.

Yops are secreted by a type III or “contact dependent” secretion mechanism. The secretion of Yops is not a constitutive process, instead Yop secretion occurs in response to specific signals associate with contacting a eukaryotic cell. The research conducted in my laboratory is aimed at understanding the role of Yop secretion in the pathogenesis of plague. Specifically, we are interested in identifying and characterizing plasmid-encoded gene products required for Yop export. In addition, we are investigating the role of YopN in the regulation of Yop export in Yersinia. Deletional inactivation of YopN (or TyeA, SycN or YscB) allows high-level expression and Yop secretion prior to contact with eukaryotic cell. We are currently using molecular genetic techniques to define the interactions and functions of YopN, TyeA, SycN and YscB in the regulation of Yop export in Yersinia.