A Plague on Host Defense

". .. the plague bacillus never dies or disappears for good;. .. it bides its time in bedrooms, cellars, trunks, and bookshelves; and perhaps the day would come when, for the bane and the enlightening of men, it would rouse up its rats again and send them forth to die in a happy city. " Albert Camus, The Plague. Few other pathogens have caused as much devastation in human history as Yersinia pestis , the etiologic agent of the plague, or the Black Death, as the disease was aptly named in the Middle Ages. Y. pestis is generally transmitted through the bites of the rat flea Xenopsylla cheopis , while the two other related pathogenic Yersinia species, Y. pseudotu-berculosis and Y. enterocolitica , are food-borne pathogens that cause various gastrointestinal syndromes (1). All three species of Yersinia are pathogenic for humans and rodents and, despite differences in the routes of entry into the host, all three infect lymphoid tissues and organs. The pathogenicity of Yersinia spp. largely results from the ability to resist innate host defense mechanisms such as phagocytosis and the induction of inflammatory responses by macrophages and neutrophils. Yersinia achieves this resistance by injecting into host cells effector proteins that can manipulate or inhibit normal immune responses. Like many other gram-negative bacterial pathogens of animals and plants, Yersinia employs a specialized secretory apparatus called the type III secretion system (TTSS) to interact with host cells (1, 2). The TTSS is a multicomponent secretion machine that injects specialized proteins (TTSS effectors) into the cytosol of the host cell where they interact with a variety of host proteins and thus manipulate cellular behavior in ways that ultimately benefit the pathogen (3). The effector proteins (collectively referred to as Yops– Yersinia outer membrane proteins) and the proteins comprising the TTSS are all encoded on a 70-kb plasmid (2). The cellular functions of the Yops are currently under intense study and fall into two general categories: proteins facilitating the translocation of Yops into the host cells, and those actually secreted into the cytosol (1, 2). Notably, YopD, YopB, and LcrV (low calcium response protein V) appear to operate in the translocation of other Yops into the cytosol whereas YopE, YopH, YopJ (Yop P in Y. en-terocolitica), YopM, YopO, and YopT function within the host cell (1, 2). The Yop proteins are Yersinia virulence factors that can interfere with phagocytosis, inhibit the antimi-crobial …