Clustered intracellular Salmonella Typhimurium Blocks Host Cell Cytokinesis
File(s)
Published version
Accepted version
Author(s)
Santos, AJM
Durkin, C
Helaine, S
Boucrot, E
Holden, DW
Type
Journal Article
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 colonise the gut epithelium, where inhibition of the cell cycle of infected cells enhances the intestinal colonisation. We found that intracellular Salmonella enterica Typhimurium induced the binucleation of a large proportion of epithelial cells by 14 hours post invasion, which 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 organising centre of infected epithelial cells. During host cell division these clustered microcolonies prevented the correct localisation 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, either resulting in 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.
Date Issued
2016-05-16
Date Acceptance
2016-05-16
Citation
Infection and Immunity, 2016, 84 (7), pp.2149-2158
ISSN
1098-5522
Publisher
American Society for Microbiology
Start Page
2149
End Page
2158
Journal / Book Title
Infection and Immunity
Volume
84
Issue
7
Copyright Statement
© 2016 Santos et al. This is an open-access article distributed under the
terms of the Creative Commons Attribution 4.0 International license.
terms of the Creative Commons Attribution 4.0 International license.
License URL
Source Volume Number
84
Subjects
Microbiology
06 Biological Sciences
11 Medical And Health Sciences
07 Agricultural And Veterinary Sciences
Publication Status
Published