![]() The capacity to survive and multiply in lymphoid tissue and to inhibit several important host immune mechanisms, including phagocytosis, is an essential virulence property of this pathogen. This permits bacterial survival and subsequent dissemination from these sites, resulting in systemic infection. Pathogenic Yersinia bind phagocytes and can impair their phagocytic capacity as well as certain inflammatory responses, ,. Common to all three Yersinia species is their ability to replicate extracellularly in lymphoid tissue where most other bacteria are effectively engulfed and destroyed by phagocytes. Also enteropathogenic Yersinia species can grow within macrophages, but if this occurs during infection, like for Y. enterocolitica are transmitted by the oral-fecal route and penetrate the intestinal epithelium and spread to the lymphatic system (first Peyer's patches and thereafter mesenteric lymph nodes) where they replicate extracellularly. pestis replicate within macrophages during the early stages of infection at peripheral host sites, ,, while extracellular growth is predominant during other stages of infection. pestis, the causative agent of plague, where bubonic plague is the most common form, is usually transmitted by the bite of a flea and spread to regional lymph nodes after which it can enter the bloodstream and spread systemically. The genus Yersinia contains three pathogenic species: Yersinia pestis, Yersinia enterocolitica and Yersinia pseudotuberculosis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. acknowledges financial support from the J. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by grants from the Swedish Research Council VR-M (521-2008-2603, H.W-W K, M.F ), and S.E.T. Received: NovemAccepted: JanuPublished: February 10, 2011Ĭopyright: © 2011 Thorslund et al. PLoS ONE 6(2):Įditor: Olivier Neyrolles, Institut de Pharmacologie et de Biologie Structurale, France (2011) The RACK1 Signaling Scaffold Protein Selectively Interacts with Yersinia pseudotuberculosis Virulence Function. Together, our data imply that the local event of Yersinia-mediated antiphagocytosis involves a step where YopK, by binding RACK1, ensures an immediate specific spatial delivery of antiphagocytic effectors leading to productive inhibition of phagocytosis.Ĭitation: Thorslund SE, Edgren T, Pettersson J, Nordfelth R, Sellin ME, Ivanova E, et al. Further, a yopK mutant unable to bind RACK1 shows an avirulent phenotype during mouse infection, suggesting that RACK1 targeting by YopK is a requirement for virulence. ![]() This resistance is not due to altered levels of translocated antiphagocytic effectors, and cells with reduced levels of RACK1 are still sensitive to the later occurring cytotoxic effect caused by the Yop effectors. Cells with downregulated RACK1 levels are protected from antiphagocytosis. pseudotuberculosis-mediated β1-integrin activation and localizes to phagocytic cups. ![]() Further, we show that YopK that can interact with the translocators, is exposed inside target cells and binds to the eukaryotic signaling protein RACK1. We present data showing that YopK influences Yop effector translocation by modulating the ratio of the pore-forming proteins YopB and YopD in the target cell membrane. We show here that the virulence protein YopK has a role in orchestrating effector translocation necessary for productive antiphagocytosis. This is called antiphagocytosis, and constitutes an important virulence feature of this pathogen since it allows survival in immune cell rich lymphoid organs. The pathogen Yersinia can resist phagocytosis by eukaryotic cells by translocating Yop effectors into the target cell cytoplasm. These effectors interfere with cellular functions in a highly regulated manner resulting in effects that are beneficial for the bacteria. Many Gram-negative bacteria use type III secretion systems to translocate effector proteins into host cells. ![]()
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