Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics - PubMed (original) (raw)

Fig. 2

Yersinia pestis virulence determinants. Y. pestis requires the three well-characterized virulence plasmids pYV/pCD1, pPla/pPCP1, and pFra/pMT1, as well as chromosomally encoded virulence factors to cause disease. Examples of cytoplasmic, cell-surface associated, and secreted virulence factors are shown. The infectious process involves adhesion to host cells mediated by Braun lipoproteins Lpp and proteins such as Ail, PsaA, and Pla. Yop effectors, including YopH, YopE, YopT, YopJ, YpkA, YopM, and YopK, are subsequently delivered through the T3SS to trigger apoptosis, inhibit phagocytosis, and block cytokine production. LPS modification and the capsular antigen F1 encoded by the caf gene further contribute to Yersinia immune escape. The expression of many of these virulence determinants is induced during the transition from the temperature of the flea midgut (26 °C) to that of the mammalian host (37 °C). Y. pestis survival in the host requires efficient metal acquisition systems. The yersiniabactin-dependent iron uptake system is encoded in the high-pathogenicity island within the pigmentation chromosomal locus pgm. Other metal transport systems, including YbtX, ZnuABC, Yfe, and Feo, also play a role in infection. Additional virulence factors have been identified by signature-tagged mutagenesis, “per-pool” mutant screening, or in vivo transcriptional profiling, e.g., YMPY1.66c, BrnQ, RbsA, GspE, NirC, CyoABCDE, PspABC, Ypo0862, Ypo1119, Ypo1120, Ypo1501, and Ypo 2884. BCAA: branched-chain amino acids, Fe: iron, LPS: lipopolysaccharide, T2SS: type-two secretion system, T3SS: type-three secretion system, T6SS: type-six secretion system, Ybt: yersiniabactin, Yop: Yersinia outer-membrane protein, Zn: zinc. Components of the illustration are not drawn to scale