Yersinia enterocolitica: Mode of Transmission, Molecular Insights of Virulence, and Pathogenesis of Infection

Abstract

Although Yersinia enterocolitica is usually transmitted through contaminated food and untreated water, occasional transmission such as human-to-human, animal-to-human and blood transfusion associated transmission have also identified in human disease. Of the six Y. enterocolitica biotypes, the virulence of the pathogenic biotypes, namely, 1B and 2-5 is attributed to the presence of a highly conserved 70-kb virulence plasmid, termed pYV/pCD and certain chromosomal genes. Some biotype 1A strains, despite lacking virulence plasmid (pYV) and traditional chromosomal virulence genes, are isolated frequently from humans with gastrointestinal diseases similar to that produced by isolates belonging known pathogenic biotypes. Y. enterocolitica pathogenic biotypes have evolved two major properties: the ability to penetrate the intestinal wall, which is thought to be controlled by plasmid genes, and the production of heat-stable enterotoxin, which is controlled by chromosomal genes.

Figure 1

Mode of transmission of Y. enterocolitica.

Figure 2

Y. enterocolitica biotypes. Y. enterocolitica biotypes are classified into three distinct group: a historically defined nonpathogenic group (biogroup 1A); a weakly pathogenic group that are unable to kill mice (biogroups 2 to 5); a highly pathogenic, mouse-lethal group (biogroup 1B). Biotype 1A strains are clustered into two clonal groups (A and B) when typed by repetitive extragenic palindrome (REP)—and enterobacterial repetitive intergenic consensus (ERIC)—PCR fngerprinting [11], and two groups when typed by fluorescent amplified fragment length polymorphism (FAFLP) [12].

Figure 3

A paradigm of “zippering” entry of a bacterial pathogen into epithelial cells. Invasin mediated binding of Yersinia to β1 integrins and internalization (adapted from [13]).

Figure 4

Physiopathological scheme of Yersinia infection (adapted from [13]). The Yops are delivered into the host cells via a type III secretion system. YopH, a tyrosine phosphatase, dephosphorylates Cas and FAK (protein tyrosine kinase) in epithelial cells, and Cas, Fyb, and SKAP-HOM in macrophages that are involved in the assembly of cytoskeletal complexes required for phagocytosis [78]; YopT modifies the Rho family GTPases by inducing redistribution of the RhoA GTPase [79]; YopE inactivates the Rho family of GTPases involved in phagocytosis [80]; YpkA binds to Rac and Rho (function unknown). These four Yops alter or disrupt the actin cytoskeleton and thereby block phagocytosis. YopJ impairs activation of MAPKKs and NF-B, which induces apoptosis and inhibits cytokine production. YopM is translocated into the nucleus (function unknown).