Yersinia virulence factors - a sophisticated arsenal for combating host defences

Abstract

The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence factor arsenal to enable them to enter, adhere to, and colonise the host while evading host defences to avoid untimely clearance. Their arsenal includes a number of adhesins that allow the invading pathogens to establish a foothold in the host and to adhere to specific tissues later during infection. When the host innate immune system has been activated, all three pathogens produce a structure analogous to a hypodermic needle. In conjunction with the translocon, which forms a pore in the host membrane, the channel that is formed enables the transfer of six ‘effector’ proteins into the host cell cytoplasm. These proteins mimic host cell proteins but are more efficient than their native counterparts at modifying the host cell cytoskeleton, triggering the host cell suicide response. Such a sophisticated arsenal ensures that yersiniae maintain the upper hand despite the best efforts of the host to counteract the infecting pathogen.

Identification of candidate infection genes from the model entomopathogenic nematode Heterorhabditis bacteriophora

“…Within eukaryotes translocons are commonly used to transfer polypeptides into the endoplasmic reticulum [26]. However, in prokaryotes, translocons can be assembled to export virulence factors outside of the cell [27, 28] While this protein may serve no other purpose than shuttling molecules into the endoplasmic reticulum, its conservation between 4 different parasites suggests that it may be needed for the transport of parasitism factors.…”

Characterizing the virulence factor YapE in Yersinia pestis.

“…YpkA/YopO, YopE, YopT and YopH play a role in the disruption of the actin cytoskeleton and target eukaryotic cell signaling components of the RhoA family of small GTPases that facilitates the inhibition of phagocytosis with the exception of YopH for the later [17,18]. Additionally, YopH disrupts both the innate and adaptive immunity pathways that are important for the virulence of all three pathogenic species in mice [17,19], in addition to inhibiting autophagy and blocking phagocytosis in macrophages [17,20,21].…”

“…Pla is a member of the omptin family of proteases that has evolved specifically for bubonic and pneumonic forms of plague [48]. Pla is able to convert plasminogen to plasmin allowing for the degradation of extracellular matrices permitting Y. pestis to quickly invade the host and migrate to draining lymph nodes [17,[49][50][51]. During subdermal or subcutaneous infection, Y. pestis expressing Pla had wide-spread bacterial foci with minimal recruitment of inflammatory cells [48,52].…”

“…Ail functions as a multi-factorial adhesin in Yersiniae [17]. During its divergence from the two enteric pathogens, it gained additional roles in the virulence of Y.…”

“…Ail has been shown to be the primary adhesin in the attachment of the T3SS to host cells in Y. pestis where its deletion exhibits significant reduction in binding to epithelial and monocytic cells [17,70].…”