The Functions of Effector Proteins in Yersinia Virulence

Abstract

Yersinia species are bacterial pathogens that can cause plague and intestinal diseases after invading into human cells through the Three Secretion System (TTSS). The effect of pathogenesis is mediated by Yersinia outer proteins (Yop) and manifested as down-regulation of the cytokine genes expression by inhibiting nuclear factor-κ-gene binding (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. In addition, its pathogenesis can also manipulate the disorder of host innate immune system and cell death such as apoptosis, pyroptosis, and autophagy. Among the Yersinia effector proteins, YopB and YopD assist the injection of other virulence effectors into the host cytoplasm, while YopE, YopH, YopJ, YopO, and YopT target on disrupting host cell signaling pathways in the host cytosols. Many efforts have been applied to reveal that intracellular proteins such as Rho-GTPase, and transmembrane receptors such as Toll-like receptors (TLRs) both play critical roles in Yersinia pathogenesis, establishing a connection between the pathogenic process and the signaling response. This review will mainly focus on how the effector proteins of Yersinia modulate the intrinsic signals in host cells and disturb the innate immunity of hosts through TTSS.

Loss of CNFY toxin-induced inflammation drives Yersinia pseudotuberculosis into persistency

“…Moreover, upregulation of YopJ, which dampens TLR-induced expression of proinflammatory cytokines by interference with the MAPK and NF k B pathways [ 64 , 65 ], and caspase-1 promoted IL-1β production [ 66 ], could overcome low translocation activity in the absence of CNF Y and help to dampen inflammation during persistence. However, this process is also accompanied by a decreased expression of other effectors such as YopE, YopH, YopM and YpkA [ 10 , 11 ] (Fig 8A ). These effectors were found to inhibit Rho GTPases and/or perturb host immune responses, including the production of certain pro-inflammatory cytokines, the maturation of caspases and the activation of the inflammasome [ 67 – 69 ].…”

“…Among them are important acute stage virulence genes, including the adhesins Ail and YadA, the cytotoxic necrotizing factor CNF Y , the virulence plasmid-encoded type III secretion system (T3SS) and the associated Yop effectors, which are highly upregulated during the initial phase of the infection [ 10 ]. The Yop effectors prevent phagocytosis by leukocytes, which is important for colonization and systemic dissemination [ 11 ]. The CNF Y toxin constitutively activates small Rho GTPases by deamidation and improves Yop translocation into host cells, thereby enhancing inflammation and tissue damage [ 12 , 13 ].…”

Antibodies Inhibiting the Type III Secretion System of Gram-Negative Pathogenic Bacteria

“…The essential effector YopM is a modulator of kinases PRK1 and PRK2. This modulation eventually leads to a reduction in pro-inflammatory cytokines lessening the effectivity of the host immune response [8]. YopM is the first effector to be recognized as a bacterial cell-penetrating protein as it can leave and re-enter host cells after translocation [127].…”

“…Some pathogens even interfere with or induce programmed cell death (Yersinia spp., Pseudomonas spp.) [8,9]. The T3SS is becoming an important anti-virulence target for many reasons.…”

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).…”