Translocated effectors of Yersinia
Introduction
The genus Yersinia includes three human pathogens. The most infamous is the black death agent Y. pestis, which causes bubonic plague when it is transmitted by the bite of a flea and pneumonic plague when it is acquired through aerosol transmission [1]. By contrast, Y. enterocolitica and Y. pseudotuberculosis are enteropathogens transmitted by consumption of contaminated food or water [2]. These two organisms cause gastrointestinal syndromes that can develop into fatal septicemia in patients with compromised or underdeveloped immune systems. Regardless of the species and type of disease that ensues, translocation of toxic virulence effectors into host cells by type III secretion (T3S) systems plays an essential role in determining the outcome of a Yersinia infection. There are two recognized groups of effector proteins delivered by T3SSs among the Yersinia; the Yops and the Ysps.
Section snippets
Yop effectors and the innate immune response
Interestingly, despite the various modes of transmission and diseases caused by the pathogenic Yersinia, they commonly have the plasmid-encoded Ysc T3SS for the delivery of six Yop effectors (YopE, YopH, YpkA/YopO, YopM, YopJ/P, and YopT) (Table 1). Efforts to determine the biochemical activities of the Yops have revealed that many targets are cellular components that influence the host innate immune response (Figure 1). This arm of the immune system serves as the front line of defense against
Ysp effectors of Y. enterocolitica Biovar 1B
While the Ysc T3SS is important for Yersinia virulence, it is now clear that some isolates of Yersinia utilize additional T3SSs to deliver virulence effectors into targeted host cells. The highly pathogenic Y. enterocolitica Biovar 1B carries the Ysa pathogenicity island (Ysa-PI) encoding a T3SS that is distinctly different from the Ysc T3SS and is more related to the Mxi-Spa T3SS of Shigella species [27, 28, 29]. The Ysa-PI is part of a larger region of the chromosome, called the plasticity
New Yersinia effectors yet to be discovered
Genomic sequencing of numerous strains of Y. pestis and Y. pseudotuberculosis have revealed a locus with the potential to encode a T3SS that is different than either the Ysc or Ysa T3SSs [37, 38]. This system resembles the Ssa T3SS of Salmonella enterica [39]. It has also been reported that this locus is present in some Y. enterocolitica serotype O:3 strains [40]. To date, no clear link between this T3SS and virulence has been established. On another front, one controversial study has suggested
Do Yersinia translocate effectors by other mechanisms?
Direct translocation of effectors into host cells by Gram-negative bacteria can additionally involve T4SSs and T6SSs. Recent genomic analysis has suggested the presence of several potential T6SSs encoded by loci dispersed among Y. pestis and Y. pseudotuberculosis genomes [43, 44]. Some of these gene-clusters could encode proteins homologous to the Hcp- and VgrG-families of secreted proteins and effectors. It has also been reported that some Y. pseudotuberculosis strains carry a plasmid
Conclusions
The Yop effectors are nearly identical between Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica. The study of pathogenic Yersinia presents an opportunity to examine how these effectors are utilized by pathogenic species causing different types of infections. The discovery of the Ysa T3SS of Y. enterocolitica Biovar 1B expands on this theme of comparative pathology by further revealing that some effectors, like YopE and YopJ/P, can contribute to disease when delivered through other
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
The authors apologize to colleagues whose work could not be cited owing to space limitations. We express our appreciation for the editorial advice of Briana Young. Work in GMY's laboratory is sponsored by grants from the National Institutes of Health, R21 AI165042 and R21 AI067676.
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Cited by (68)
Yersinia enterocolitica
2023, Molecular Medical Microbiology, Third EditionThe role of pyroptosis in gastrointestinal cancer and immune responses to intestinal microbial infection
2019, Biochimica et Biophysica Acta - Reviews on CancerCitation Excerpt :Some Gram-negative genus, e.g. Yersinia and Aeromonas with T3SS exert their virulence by modulating pyroptosis or apoptosis [164]. In host immune responses to bacterial invasion, activation of such signaling pathways as NF-κB and MAPK induce the expression of proinflammatory cytokines like IL-12,-18 via the effectors of T3SS, T2SS or T6SS in both genus [165]. For instance, studies showed the T3SS effector, Yersinia outer membrane protein J (YopJ) impeded NF-κB and MAPK signaling via acetyltransferase and deubiquitinase, and finally activated apoptosis [166,167].
Yersinia Species
2017, Principles and Practice of Pediatric Infectious DiseasesNews and views on protein secretion systems
2015, The Comprehensive Sourcebook of Bacterial Protein ToxinsMicrobial strategies for antagonizing Toll-like-receptor signal transduction
2015, Current Opinion in Immunology