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    Clustered Intracellular Salmonella enterica Serovar Typhimurium blocks host cell cytokinesis

    Santos, A.J.M. and Durkin, C.H. and Helaine, S. and Boucrot, Emmanuel and Holden, D.W. and McCormick, B.A. (2016) Clustered Intracellular Salmonella enterica Serovar Typhimurium blocks host cell cytokinesis. Infection and Immunity 84 (7), pp. 2149-2158. ISSN 0019-9567.

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    Abstract

    Several bacterial pathogens and viruses interfere with the cell cycle of their host cells to enhance virulence. This is especially apparent in bacteria that colonize the gut epithelium, where inhibition of the cell cycle of infected cells enhances the intestinal colonization. We found that intracellular Salmonella enterica serovar Typhimurium induced the binucleation of a large proportion of epithelial cells by 14 h postinvasion and that the effect was dependent on an intact Salmonella pathogenicity island 2 (SPI-2) type 3 secretion system. The SPI-2 effectors SseF and SseG were required to induce binucleation. SseF and SseG are known to maintain microcolonies of Salmonella-containing vacuoles close to the microtubule organizing center of infected epithelial cells. During host cell division, these clustered microcolonies prevented the correct localization of members of the chromosomal passenger complex and mitotic kinesin-like protein 1 and consequently prevented cytokinesis. Tetraploidy, arising from a cytokinesis defect, is known to have a deleterious effect on subsequent cell divisions, resulting in either chromosomal instabilities or cell cycle arrest. In infected mice, proliferation of small intestinal epithelial cells was compromised in an SseF/SseG-dependent manner, suggesting that cytokinesis failure caused by S. Typhimurium delays epithelial cell turnover in the intestine.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Research Centre: Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 21 Jul 2016 13:50
    Last Modified: 27 Jul 2019 16:36
    URI: http://eprints.bbk.ac.uk/id/eprint/15769

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