title: Clustered Intracellular Salmonella enterica Serovar Typhimurium Blocks Host Cell Cytokinesis.
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.
authors.affiliation: Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom antonio.santos@crg.eu d.holden@imperial.ac.uk.|Graduate Program in Areas of Basic and Applied Biology (GABBA), University of Porto, Porto, Portugal.
authors.forename: António J M
authors.initials: AJM
authors.lastname: Santos
authors.affiliation: Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Durkin
authors.affiliation: Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Sophie
authors.initials: S
authors.lastname: Helaine
authors.affiliation: Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Boucrot
authors.affiliation: Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom antonio.santos@crg.eu d.holden@imperial.ac.uk.
authors.forename: David W
authors.initials: DW
authors.lastname: Holden
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D048749:Cytokinesis; D005260:Female; D054884:Host-Pathogen Interactions; D007421:Intestine, Small / Q000382:microbiology / Q000473:pathology; D051379:Mice; D012480:Salmonella Infections / Q000378:metabolism / Q000382:microbiology; D012486:Salmonella typhimurium / Q000502:physiology*; D000069296:Type III Secretion Systems / Q000378:metabolism
chemical_list: D000069296:Type III Secretion Systems