To facilitate attachment, invasion, and colonization of its host, this bacterium possesses many
virulence factors. Superantigens, bacterial adhesions, and the actions of Yops (which are bacterial proteins once thought to be "
Yersinia outer membrane proteins") that are encoded on the "
plasmid for
Yersinia virulence" – commonly known as the pYV – cause host pathogenesis and allow the bacteria to live parasitically.
pYV The 70-kb pYV is critical to
Yersinia's pathogenicity, since it contains many
genes known to encode virulence factors and its loss gives avirulence of all
Yersinia species. The core region also includes
yopN,
yopB,
yopD,
tyeA,
lcrG, and
lcrV, which also regulate Yops
gene expression and help to translocate secretory Yops to the target cell. Secretion is regulated in this fashion so that proteins are not expelled into the
extracellular matrix and elicit an
immune response. Since this pathway gives secretion selectivity, it is a virulence factor.
Effector Yops In contrast to the
ysc and
yop genes listed above, the Yops that act directly on host cells to cause cytopathologic effects – "effector Yops" – are encoded by
pYV genes external to this core region. By causing actin filament depolymerisation, YopE, YopT, and YpkA resist
endocytosis by intestinal cells and
phagocytosis while giving cytotoxic changes in the host cell. YopT targets Rho GTPase, commonly named "RhoA", and uncouples it from the membrane, leaving it in an inactive RhoA-GDI (guanine nucleotide dissociation inhibitor)-bound state whereas YopE and YpkA convert Rho proteins to their inactive GDP-bound states by expressing GTPase activity. or undermine host cell immune response signal cascades since YpkA is targeted to the cytoplasmic side of the host cell membrane. YopH acts on host focal adhesion sites by dephosphorylating several
phosphotyrosine residues on
focal adhesion kinase (FAK) and the focal adhesion proteins
paxillin and p130. Since FAK phosphorylation is involved in uptake of yersiniae as well as
T cell and
B cell responses to antigen-binding, leading to macrophage
apoptosis. By secretion through a type III pathway and localization in the nucleus by a vesicle-associated, microtubule-dependent method, YopM may alter host cell growth by binding to RSK (ribosomal S6 kinase), which regulates cell cycle regulation genes.
opsonisation-resisting, phagocytosis-resisting, and
respiratory burst-resisting functions in
Y. pseudotuberculosis due to a
frameshift mutation by a single base-pair deletion in
yadA in comparison to
yadA in
Y. enterocolitica, yet it still is secreted by type III secretion. The
yop genes,
yadA,
ylpA, and the
virC operon are considered the "Yop regulon" since they are coregulated by pYV-encoded VirF.
virF is in turn thermoregulated. At 37 degrees Celsius, chromosomally encoded Ymo, which regulates
DNA supercoiling around the
virF gene, changes conformation, allowing for virF expression, which then up-regulates the Yop regulon.
Adhesion Y. pseudotuberculosis adheres strongly to intestinal cells via chromosomally encoded proteins Through this binding, the integrins cluster, thereby activating FAK, and causing a corresponding reorganization of the cytoskeleton. while interfering with the binding of complement on the bacterial surface. To increase binding specificity, the fibrillar pH6 antigen targets bacteria to target intestinal cells only when thermoinduced.
Superantigens Certain strains of
Yersinia pseudotuberculosis express a
superantigenic exotoxin, YPM, or the
Y. pseudotuberculosis-derived mitogen, from the chromosomal
ypm gene. YPM specifically binds and causes the proliferation of T lymphocytes expressing the Vβ3, Vβ7, Vβ8, Vβ9, Vβ13.1, and Vβ13.2 variable regions with
CD4+ T cell preference, although activation of some CD8+
T cells occurs. Since administering anti-
TNF-α and anti-
IFN-γ monoclonal
antibodies neutralizes YPM toxicity
in vivo, and are correlated with Izumi fever and
Kawasaki disease. Although the superantigen poses the greatest threat to host health, all virulence factors contribute to
Y. pseudotuberculosis viability
in vivo and define the bacterium's pathogenic characteristics.
Y. pseudotuberculosis can live extracellularly due to its formidable mechanisms of phagocytosis and
opsonisation resistance through the expression of Yops and the type III pathway;
Function Yersinia pseudotuberculosis-derived mitogens (YpM) are
superantigens, which are able to excessively activate
T cells by
binding to the T cell
receptor. Since YpM can activate large numbers of the T cell population, this leads the release of inflammatory
cytokines.
Structure Members of this family of
Yersinia pseudotuberculosis mitogens adopt a sandwich
structure consisting of 9 strands in two beta sheets, in a
jelly roll fold topology. YpM molecular weight is about 14 kDa. Structurally, it is unlike any other superantigen, but is remarkably similar to the
tumour necrosis factor and viral capsid proteins. This suggests a possible evolutionary relationship.
Subfamilies Some highly similar homologous variants of YPM have been characterized, including YPMa, YPMb, and YPMc.
Small non-coding RNA Numerous
bacterial small non-coding RNAs have been identified to play regulatory functions. Some can regulate the virulence genes. 150 unannotated sRNAs were identified by sequencing of
Y. pseudotuberculosis RNA libraries from bacteria grown at 26 °C and 37 °C, suggesting they may play a role in pathogenesis. By using single-molecule
fluorescence in situ hybridisation smFISH technique it was shown that the number of YSR35 RNA increased 2.5 times upon temperature shift from 25 °C to 37 °C. Another study uncovered that a temperature-induced global reprogramming of central metabolic functions are likely to support intestinal colonization of the pathogen. Environmentally controlled regulatory RNAs coordinate control of metabolism and virulence allowing rapid adaptation and high flexibility during life-style changes. High-throughput RNA structure probing identified many thermoresponsive RNA structures. == See also ==