Integral and peripheral association of proteins and protein complexes with Yersinia pestis inner and outer membranes

Yersinia pestis, a Gram-negative bacterium, is the causative agent of the bubonic and pneumonic plague. The pathogenic lifestyle of this microbe involves two distinct life stages, one in the flea vector, the other in mammalian hosts, primarily rodents [1]. Humans are a dead-end host and not part of the flea-mammal cycle. Y. pestis strains associated with high virulence have been divided into three classical biovars (antiqua, mediaevalis and orientalis) based on differences in their abilities to ferment glycerol and reduce nitrate. A fourth biovar (microtus) has been proposed on the basis of low virulence and reduced transmission [2-4]. Complete DNA sequence data exist for the genomes of each of these four biovars [5-8]. The gene organization and complete DNA sequences of three Y. pestis virulence-associated plasmids were also determined [9,10]. The pCD1 plasmid, shared with other human pathogenic Yersinia species, encodes a suite of proteins required for a functional type III secretion system (T3SS) and host infection. A temperature increase from 26–30 to 37°C and host cell contact or a low Ca2+ concentration induce expression of these proteins [11]. Most Y. pestis strains harbor two unique plasmids, pPCP1 and pMT1, not present in Y. pseudotuberculosis. These plasmids encode factors such as the plasminogen activator protease (Pla), required for mammalian pathogenesis [12], the Yersinia murine toxin (Ymt), required for colonization of the mid-gut of fleas [13,14], and the F1 capsular antigen (Caf1) [15]. The F1 antigen causes in vitro resistance to phagocytosis, but its role in mammalian virulence is unclear [16]. In addition, the genetically unstable chromosomal 102-kb pgm locus is important for full virulence of the bubonic plague in mammals and for transmission via blocked fleas [17,18]. It encodes the yersiniabactin siderophore-dependent iron transport (Ybt) system [19,20] and the Hms-dependent biofilm system. Biofilm formation allows colonization of the flea pro