Bacillus cereus cytotoxin K triggers gasdermin D-dependent pyroptosis

Abstract Bacillus cereus is well known as a causative agent of foodborne gastrointestinal diseases and systemic non-gastrointestinal diseases. We have recently identified a pathogenic B. cereus (named H2) from a deep-sea cold-seep. H2 possesses the pyroptosis-inducing capacity and contains a number...

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Main Authors: Yan Zhao, Li Sun
Format: Article
Language:English
Published: Nature Publishing Group 2022-07-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-022-01091-5
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author Yan Zhao
Li Sun
author_facet Yan Zhao
Li Sun
author_sort Yan Zhao
collection DOAJ
description Abstract Bacillus cereus is well known as a causative agent of foodborne gastrointestinal diseases and systemic non-gastrointestinal diseases. We have recently identified a pathogenic B. cereus (named H2) from a deep-sea cold-seep. H2 possesses the pyroptosis-inducing capacity and contains a number of enterotoxins including cytotoxin K (CytK). In the present work, we examined the cytotoxicity of the CytK of H2 to human macrophages. CytK bound macrophages by interaction with the plasma membrane and caused cellular structure damage. CytK−cell interaction triggered rapid pyroptosis mediated by caspase 1-activated gasdermin D (GSDMD). CytK-induced pyroptosis required NLRP3 inflammasome activation, K+ efflux, and intracellular Ca2+ accumulation. CytK exhibited apparent binding to several cytomembrane lipids, in particular phosphatidic acid, which proved to be essential to CytK-elicited cell death. Together, these results add new insights into the cytotoxic mechanism of CytK.
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spelling doaj.art-049fc047ce9d47dabf8af18136c6d2652022-12-22T01:00:01ZengNature Publishing GroupCell Death Discovery2058-77162022-07-01811810.1038/s41420-022-01091-5Bacillus cereus cytotoxin K triggers gasdermin D-dependent pyroptosisYan Zhao0Li Sun1CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of SciencesCAS and Shandong Province Key Laboratory of Experimental Marine Biology, Institute of Oceanology, CAS Center for Ocean Mega-Science, Chinese Academy of SciencesAbstract Bacillus cereus is well known as a causative agent of foodborne gastrointestinal diseases and systemic non-gastrointestinal diseases. We have recently identified a pathogenic B. cereus (named H2) from a deep-sea cold-seep. H2 possesses the pyroptosis-inducing capacity and contains a number of enterotoxins including cytotoxin K (CytK). In the present work, we examined the cytotoxicity of the CytK of H2 to human macrophages. CytK bound macrophages by interaction with the plasma membrane and caused cellular structure damage. CytK−cell interaction triggered rapid pyroptosis mediated by caspase 1-activated gasdermin D (GSDMD). CytK-induced pyroptosis required NLRP3 inflammasome activation, K+ efflux, and intracellular Ca2+ accumulation. CytK exhibited apparent binding to several cytomembrane lipids, in particular phosphatidic acid, which proved to be essential to CytK-elicited cell death. Together, these results add new insights into the cytotoxic mechanism of CytK.https://doi.org/10.1038/s41420-022-01091-5
spellingShingle Yan Zhao
Li Sun
Bacillus cereus cytotoxin K triggers gasdermin D-dependent pyroptosis
Cell Death Discovery
title Bacillus cereus cytotoxin K triggers gasdermin D-dependent pyroptosis
title_full Bacillus cereus cytotoxin K triggers gasdermin D-dependent pyroptosis
title_fullStr Bacillus cereus cytotoxin K triggers gasdermin D-dependent pyroptosis
title_full_unstemmed Bacillus cereus cytotoxin K triggers gasdermin D-dependent pyroptosis
title_short Bacillus cereus cytotoxin K triggers gasdermin D-dependent pyroptosis
title_sort bacillus cereus cytotoxin k triggers gasdermin d dependent pyroptosis
url https://doi.org/10.1038/s41420-022-01091-5
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