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oai:recercat.cat:10230/309052025-12-12T01:57:11Zcom_2072_6col_2072_452952
RECERCAT author Santos, António J. M. author Durkin, Charlotte H. author Helaine, Sophie author Boucrot, Emmanuel author Holden, David W. 2017-04-26T10:07:00Z2017-04-26T10:07:00Z2016 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.This work was funded by the Wellcome Trust, Medical Research Council (MRC), the Biotechnology and Biological Sciences Research Council (BBSRC), and the Ministry of Education and Science | Fundação para a Ciência e a Tecnologia (FCT) (SFRH/BD/33545/2008). © American Society for Microbiology. Copyright © 2016 Santos et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Cellular Microbiology Pathogen-Host Cell Molecular Interactions Clustered Intracellular Salmonella enterica Serovar Typhimurium Blocks Host Cell Cytokinesis info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion