The role of the phoPQ operon in the pathogenesis of the fully virulent CO92 strain of Yersinia pestis and the IP32953 strain of Yersinia pseudotuberculosis

Identification of host factors required for Yersinia pestis macrophage intracellular survival and their impact on vacuole maturation, acidification and trafficking.

“…Several in vivo studies indicate that intracellular survival in macrophages is important for colonization of the mammalian host [52,62,90]. Ye et al demonstrated selective depletion of Gr1 + macrophage and dendritic cells in transgenic MaFIA mice lessens the severity of plague infection [52].…”

“…Additionally, macrophages from canines (a species relatively resistant to plague infection) are better equipped to kill intracellular Y. pestis than rodent macrophages (the natural reservoir for plague) [62,91]. Finally, in vivo infection studies with Y. pestis phoP mutants, which are defective for intracellular survival, have reported extended times to death for the phoP mutant compared to wildtype Y. pestis [90]. These data suggest intracellular survival of Y. pestis also contributes to early immune evasion and pathogenesis.…”

“…During this transition the bacteria is not expressing temperature dependent mammalian specific virulence factors, such as the T3SS, and is easily killed by neutrophils. Y. pestis ΔphoP mutants are defective for intracellular survival and exhibit a higher LD50 with an extended time to death [56,83,90,151]. The role of macrophages during pathogenesis is further emphasized by findings that Y. pestis predominately associates with macrophages and not neutrophils in infected rodents and nonhuman primates [49,53,58,84].…”

“…Ye and colleagues further showed lower bacterial burdens in transgenic MaFIA mice selectively depleted of macrophage/dendritic cell populations, suggesting that macrophages are required to establish acute infection [52]. Y. pestis phoPQ mutants, which are defective for intracellular survival, are also attenuated during subcutaneous infection of BALB/c (75-fold change in LD50) and Swiss Webster mice (no change in LD50 but a significant delay in time to death for mutant infected animals) [56,90]. Moreover, macrophages isolated from canines, a species that are relatively resistant to plague [91], are significantly more capable in killing Y. pestis than macrophages isolated from laboratory mice, a species highly susceptible to plague, suggesting that the ability of macrophages to kill Y. pestis may contribute to resistance to infection [62].…”

Characterizing the virulence factor YapE in Yersinia pestis.

“…This has been exhibited by lower bacterial burden when animals were depleted for dendritic/macrophage populations during plague infection and survival defect, in macrophages, by a phoPQ mutant [30,80,[82][83][84][85]. yapE transcription levels are very low during in vitro growth [74].…”