Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Guenther, Saskia D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fritsch, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Seeger, Jens M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schiffmann, Lars M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Snipas, Scott J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Coutelle, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Kufer, Thomas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Higgins, Paul G. UNSPECIFIED orcid.org/0000-0001-8677-9454 UNSPECIFIED Hornung, Veit UNSPECIFIED UNSPECIFIED UNSPECIFIED Bernardini, Maria L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoening, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Salvesen, Guy S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, Hamid UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language NONCANONICAL INFLAMMASOME ACTIVATION; NF-KAPPA-B; CELL-DEATH; SHIGELLA-FLEXNERI; O-ANTIGEN; FRANCISELLA-TULARENSIS; HOST; XIAP; LPS; RECOGNITION Multiple languages Microbiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12401