Yersinia pseudotuberculosis (Yptb), a gram-negative bacterium, is known to cause severe intestinal infections that can disseminate to internal organs, particularly the liver. In this essay, we summarize the current understanding of the mechanisms by which Yptb utilizes its plasmid- and chromosome-encoded proteins to evade host immune responses and promote bacterial colonization of the liver. This review focuses on the immunomodulatory effects of Yptb toxins, specifically their role in modulating phagocyte activity and promoting bacterial survival.
Yersinia pseudotuberculosis and its Pathogenicity
Yptb primarily causes intestinal infections, with outbreaks reported in cold temperate regions of Europe and North America. However, Far East scarlet-like fever (FESLF), a severe variant of Yptb infection, has been noted in Russia and Japan, characterized by a higher incidence of liver damage. Yptb disseminates from the intestine to organs such as the liver via the bloodstream, where it persists and causes abscesses, hepatitis, and sepsis.
Bacterial Defense Mechanisms: Plasmid-encoded Effector Proteins
Yptb expresses several plasmid-encoded effector proteins (Yops) belonging to the Type III secretion system (T3SS), which are critical for suppressing phagocytic activity. These Yops, including YopM, YopH, YopE, and YopT, are injected into host cells, primarily phagocytes, to disrupt their function. The master regulator LcrF controls the expression of these effector proteins in response to temperature changes and other environmental stimuli.
Role of YopM in Bacterial Colonization
YopM, a 42-54 kDa protein, promotes Yptb colonization of the liver and other organs by reducing inflammation and stimulating the production of anti-inflammatory cytokines, particularly interleukin (IL)-10. YopM promotes nuclear translocation of STAT3, leading to increased IL-10 expression, which aids bacterial survival. Studies have shown that the presence of YopM significantly contributes to liver colonization, while its absence results in reduced bacterial load.
YopM selectively targets polymorphonuclear leukocytes (PMNs) and inflammatory Kupffer cells in the liver, promoting their apoptotic death. This proapoptotic effect is mediated by caspase-3 and is specific to the liver, suggesting a tissue-specific mechanism of action. Additionally, YopM has been found to reduce the numbers of dendritic cells in the liver, further modulating the immune response.
Chromosome-encoded Toxins and Their Role
In addition to plasmid-encoded toxins, chromosome-encoded proteins such as YPM, CNF Y, and TsTYp also play a significant role in Yptb virulence. These toxins have been identified primarily in Far Eastern strains of Yptb, which exhibit a higher degree of virulence and tissue damage. These toxins, through various mechanisms, contribute to the suppression of host immune responses and promotion of bacterial colonization.
Conclusions and Future Directions
This review highlights the intricate mechanisms employed by Yptb to evade host immune responses and promote bacterial colonization of the liver. The plasmid- and chromosome-encoded toxins play pivotal roles in modulating phagocyte activity and promoting bacterial survival. A comprehensive understanding of these immunomodulatory effects will pave the way for developing novel therapeutic strategies to combat Yptb infections and associated liver damage.
Future research should focus on elucidating the detailed molecular mechanisms of Yptb toxins, particularly their interactions with host immune cells and signaling pathways. Additionally, studies comparing the virulence of different Yptb strains from various geographical regions will provide valuable insights into the evolution and epidemiology of this pathogen. The development of novel antimicrobials targeting these toxins may offer effective treatment options for patients with Yptb infections.
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The study was recently published in the Gene Expression.
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