Guenther, Saskia D., Fritsch, Melanie, Seeger, Jens M., Schiffmann, Lars M., Snipas, Scott J., Coutelle, Maria, Kufer, Thomas A., Higgins, Paul G. ORCID: 0000-0001-8677-9454, Hornung, Veit, Bernardini, Maria L., Hoening, Stefan, Kroenke, Martin, Salvesen, Guy S. and Kashkar, Hamid (2020). Cytosolic Gram-negative bacteria prevent apoptosis by inhibition of effector caspases through lipopolysaccharide. NAT. MICROBIOL, 5 (2). S. 354 - 385. LONDON: NATURE PUBLISHING GROUP. ISSN 2058-5276

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Abstract

The cytosolic appearance and propagation of bacteria cause overwhelming cellular stress responses that induce apoptosis under normal conditions. Therefore, successful bacterial colonization depends on the ability of intracellular pathogens to block apoptosis and to safeguard bacterial replicative niches. Here, we show that the cytosolic Gram-negative bacterium Shigella flexneri stalls apoptosis by inhibiting effector caspase activity. Our data identified lipopolysaccharide (LPS) as a bona fide effector caspase inhibitor that directly binds caspases by involving its O-antigen (O Ag) moiety. Bacterial strains that lacked the O Ag or failed to replicate within the cytosol were incapable of blocking apoptosis and exhibited reduced virulence in a murine model of bacterial infection. Our findings demonstrate how Shigella inhibits pro-apoptotic caspase activity, effectively delays coordinated host-cell demise and supports its intracellular propagation. Next to the recently discovered pro-inflammatory role of cytosolic LPS, our data reveal a distinct mode of LPS action that, through the disruption of the early coordinated non-lytic cell death response, ultimately supports the inflammatory breakdown of infected cells at later time points. The lipopolysaccharide of the intracellular pathogen Shigella, in particular its O antigen, interacts with caspases and blocks their activation to prevent apoptosis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Guenther, Saskia D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fritsch, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seeger, Jens M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schiffmann, Lars M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Snipas, Scott J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coutelle, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kufer, Thomas A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Higgins, Paul G.UNSPECIFIEDorcid.org/0000-0001-8677-9454UNSPECIFIED
Hornung, VeitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bernardini, Maria L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoening, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroenke, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salvesen, Guy S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kashkar, HamidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-124014
DOI: 10.1038/s41564-019-0620-5
Journal or Publication Title: NAT. MICROBIOL
Volume: 5
Number: 2
Page Range: S. 354 - 385
Date: 2020
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2058-5276
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NONCANONICAL INFLAMMASOME ACTIVATION; NF-KAPPA-B; CELL-DEATH; SHIGELLA-FLEXNERI; O-ANTIGEN; FRANCISELLA-TULARENSIS; HOST; XIAP; LPS; RECOGNITIONMultiple languages
MicrobiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/12401

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