Imperial College London
Alternate

ProfessorDavidHolden

Faculty of Medicine, Department of Infectious Disease

Professor
 
 
 
//

Contact

 

+44 (0)20 7594 3073d.holden

 
 
//

Location

 

221Flowers buildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Santos:2016:10.1128/IAI.00062-16,
author = {Santos, AJM and Durkin, C and Helaine, S and Boucrot, E and Holden, DW},
doi = {10.1128/IAI.00062-16},
journal = {Infection and Immunity},
pages = {2149--2158},
title = {Clustered intracellular Salmonella Typhimurium Blocks Host Cell Cytokinesis},
url = {http://dx.doi.org/10.1128/IAI.00062-16},
volume = {84},
year = {2016}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Santos,AJM
AU  - Durkin,C
AU  - Helaine,S
AU  - Boucrot,E
AU  - Holden,DW
DO  - 10.1128/IAI.00062-16
EP  - 2158
PY  - 2016///
SN  - 1098-5522
SP  - 2149
TI  - Clustered intracellular Salmonella Typhimurium Blocks Host Cell Cytokinesis
T2  - Infection and Immunity
UR  - http://dx.doi.org/10.1128/IAI.00062-16
UR  - http://hdl.handle.net/10044/1/33067
VL  - 84
ER  -
Download