Translocated effectors of Yersinia

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Currently, all known translocated effectors of Yersinia are delivered into host cells by type III secretion systems (T3SSs). Pathogenic Yersinia maintain the plasmid-encoded Ysc T3SS for the specific delivery of the well-studied Yop effectors. New horizons for effector biology have opened with the discovery of the Ysps of Y. enterocolitica Biovar 1B, which are translocated into host cells by the chromosome-endoded Ysa T3SS. The reported arsenal of effectors is likely to expand since genomic analysis has revealed gene-clusters in some Yersinia that code for other T3SSs. These efforts also revealed possible type VI secretion (T6S) systems, which may indicate that translocation of effectors occurs by multiple mechanisms.

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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