Abstract
Many Gram-negative bacteria use type III secretion systems to translocate effector proteins into host cells. These effectors interfere with cellular functions in a highly regulated manner resulting in effects that are beneficial for the bacteria. The pathogen Yersinia can resist phagocytosis by eukaryotic cells by translocating Yop effectors into the target cell cytoplasm. This is called antiphagocytosis, and constitutes an important virulence feature of this pathogen since it allows survival in immune cell rich lymphoid organs. We show here that the virulence protein YopK has a role in orchestrating effector translocation necessary for productive antiphagocytosis. 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. Further, we show that YopK that can interact with the translocators, is exposed inside target cells and binds to the eukaryotic signaling protein RACK1. This protein is engaged upon Y. pseudotuberculosis-mediated β1-integrin activation and localizes to phagocytic cups. Cells with downregulated RACK1 levels are protected from antiphagocytosis. 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. 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. 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.
Highlights
The genus Yersinia contains three pathogenic species: Yersinia pestis, Yersinia enterocolitica and Yersinia pseudotuberculosis [1]
We have previously shown that hemolysis is induced to a much greater extent by a yopK null mutant of Y. pseudotuberculosis than by the corresponding isogenic wild-type strain [24]
The Y. pseudotuberculosis translocation pore consists of the two hydrophobic translocator proteins YopB and YopD, which are inserted into the host cell membrane [37,38,39]
Summary
The genus Yersinia contains three pathogenic species: Yersinia pestis, Yersinia enterocolitica and Yersinia pseudotuberculosis [1]. The enteropathogenic species Y. pseudotuberculosis and 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 [8,9]. Pathogenic Yersinia bind phagocytes and can impair their phagocytic capacity as well as certain inflammatory responses [11,12,13,14,15]. This permits bacterial survival and subsequent dissemination from these sites, resulting in systemic infection [16]. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
