Imperial College London
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ProfessorGadFrankel

Faculty of Natural Sciences, Department of Life Sciences

Professor of Molecular Pathogenesis
 
 
 
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Contact

 

+44 (0)20 7594 5253g.frankel

 
 
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Location

 

1.46Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zhong:2020:10.1371/journal.pbio.3000986,
author = {Zhong, Q and Roumeliotis, T and Kozik, Z and Cepeda-Molero, M and Angel, Fernandez L and Shenoy, AR and Bakal, C and Frankel, G and Choudhary, JS},
doi = {10.1371/journal.pbio.3000986},
journal = {PLoS Biology},
title = {Clustering of Tir during enteropathogenic E. coli infection triggers calcium influx-dependent pyroptosis in intestinal epithelial cells},
url = {http://dx.doi.org/10.1371/journal.pbio.3000986},
volume = {18},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Clustering of the enteropathogenic Escherichia coli (EPEC) type III secretion system (T3SS) effector translocated intimin receptor (Tir) by intimin leads to actin polymerisation and pyroptotic cell death in macrophages. The effect of Tir clustering on the viability of EPEC-infected intestinal epithelial cells (IECs) is unknown. We show that EPEC induces pyroptosis in IECs in a Tir-dependent but actin polymerisation-independent manner, which was enhanced by priming with interferon gamma (IFNγ). Mechanistically, Tir clustering triggers rapid Ca2+ influx, which induces lipopolysaccharide (LPS) internalisation, followed by activation of caspase-4 and pyroptosis. Knockdown of caspase-4 or gasdermin D (GSDMD), translocation of NleF, which blocks caspase-4 or chelation of extracellular Ca2+, inhibited EPEC-induced cell death. IEC lines with low endogenous abundance of GSDMD were resistant to Tir-induced cell death. Conversely, ATP-induced extracellular Ca2+ influx enhanced cell death, which confirmed the key regulatory role of Ca2+ in EPEC-induced pyroptosis. We reveal a novel mechanism through which infection with an extracellular pathogen leads to pyroptosis in IECs.
AU  - Zhong,Q
AU  - Roumeliotis,T
AU  - Kozik,Z
AU  - Cepeda-Molero,M
AU  - Angel,Fernandez L
AU  - Shenoy,AR
AU  - Bakal,C
AU  - Frankel,G
AU  - Choudhary,JS
DO  - 10.1371/journal.pbio.3000986
PY  - 2020///
SN  - 1544-9173
TI  - Clustering of Tir during enteropathogenic E. coli infection triggers calcium influx-dependent pyroptosis in intestinal epithelial cells
T2  - PLoS Biology
UR  - http://dx.doi.org/10.1371/journal.pbio.3000986
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000605331900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/85926
VL  - 18
ER  -
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