Yersiniatype III effectors perturb host innate immune responses

Abstract

The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type Ⅲ secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia effector proteins and their contribution to Yersinia pathogenesis.

Modern Views on Molecular Mechanisms of Plague Pathogenesis

“…находясь внутри макрофагов, бактерии синте-зируют компоненты системы секреции третьего типа (T3SS), которые многие годы были и остаются объ-ектом пристального внимания ученых [32,33]. T3SS, кодируемая плазмидой кальций-зависимости (pCD1), состоит из 25 белков, которые образуют подобную шприцу инжектисому, пронизывающую обе мембра-ны и образующую иглу на поверхности бактерий.…”

A rare case of enteric and systemic Yersinia enterocolitica infection in a chronic, not iron-overloaded dialysis patient

“…Haemodialysis patients are chronically iron deficient and iron supplementation is routinely administered to maintain an iron appropriate level. Iron is an essential growth factor of bacteria for multiplication in the host, and, on the contrary, evidences showed that iron supplementation is harmful for the host defence mechanisms, oxygen transport, deoxy ribonucleotide synthesis, and redox reactions (6,28,35). In haemodialysis patients, various authors reported high incidence of iron-overload (8,13,26).…”

“…In haemodialysis patients, various authors reported high incidence of iron-overload (8,13,26). Y. enterocolitica requires iron for growth and it is able to accelerate the proliferation using exogenous chelators as source of iron in patients showing an iron-overloaded state or receiving an iron-chelating therapy (6,13,26,28). Y. enterocolitica group is traditionally divided in 6 biogroups based on phenotypic features, and into more than 57 O serogroups based on their (9).…”

Characterizing the virulence factor YapE in Yersinia pestis.

“…Comparable to YopJ, YopM has been shown to block mature caspase-1 activity inhibiting the recruitment of pro-caspase-1 to the inflammasome complex [32][33][34]. Loss of the T3SS or the pCD1 plasmid results in complete attenuation of all three pathogenic species in mice [18]. This further validates the importance that the T3SS is vital for the virulence of the bacteria.…”

“…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].…”