@article{Mylona:2021:10.1111/cmi.13306,
author = {Mylona, E and Sanchez, Garrido J and Nguyen, Hoang Thu T and Dongol, S and Karkey, A and Baker, S and Shenoy, AR and Frankel, G},
doi = {10.1111/cmi.13306},
journal = {Cellular Microbiology},
pages = {1--14},
title = {Very long O-antigen chains of Salmonella Paratyphi A inhibit inflammasome activation and pyroptotic cell death},
url = {http://dx.doi.org/10.1111/cmi.13306},
volume = {23},
year = {2021}
}

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TY  - JOUR
AB  - Salmonella Paratyphi A (SPtA) remains one of the leading causes of enteric (typhoid) fever. Yet, despite the recent increased rate of isolation from patients in Asia, our understanding of its pathogenesis is incomplete. Here we investigated inflammasome activation in human macrophages infected with SPtA. We found that SPtA induces GSDMDmediated pyroptosis via activation of caspase1, caspase4 and caspase8. Although we observed no cell death in the absence of a functional Salmonella pathogenicity island1 (SPI1) injectisome, HilAmediated overexpression of the SPI1 regulon enhances pyroptosis. SPtA expresses FepE, an LPS Oantigen length regulator, which induces the production of very long Oantigen chains. Using a ΔfepE mutant we established that the very long Oantigen chains interfere with bacterial interactions with epithelial cells and impair inflammasomemediated macrophage cell death. Salmonella Typhimurium (STm) serovar has a lower FepE expression than SPtA, and triggers higher pyroptosis, conversely, increasing FepE expression in STm reduced pyroptosis. These results suggest that differential expression of FepE results in serovarspecific inflammasome modulation, which mirrors the pro and antiinflammatory strategies employed by STm and SPtA, respectively. Our studies point towards distinct mechanisms of virulence of SPtA, whereby it attenuates inflammasomemediated detection through the elaboration of very long LPS Opolysaccharides.
AU  - Mylona,E
AU  - Sanchez,Garrido J
AU  - Nguyen,Hoang Thu T
AU  - Dongol,S
AU  - Karkey,A
AU  - Baker,S
AU  - Shenoy,AR
AU  - Frankel,G
DO  - 10.1111/cmi.13306
EP  - 14
PY  - 2021///
SN  - 1462-5814
SP  - 1
TI  - Very long O-antigen chains of Salmonella Paratyphi A inhibit inflammasome activation and pyroptotic cell death
T2  - Cellular Microbiology
UR  - http://dx.doi.org/10.1111/cmi.13306
UR  - https://onlinelibrary.wiley.com/doi/10.1111/cmi.13306
UR  - http://hdl.handle.net/10044/1/86330
VL  - 23
ER  - 

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