Clostridium innocuum, an emerging pathogen that induces lipid raft-mediated cytotoxicity

Hui Yu Wu, Chia Jung Kuo, Chia Huei Chou, Mao Wang Ho, Chyi Liang Chen, Tsui Shan Hsu, Ying Chu Chen, Chuan Chiang-Ni, Yi Ywan M. Chen, Cheng Hsun Chiu*, Chih Ho Lai

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

Clostridium innocuum is an emerging spore-forming anaerobe that is often observed in Clostridioides difficile-associated inflammatory bowel disease (IBD) exacerbations. Unlike C. difficile, C. innocuum neither produces toxins nor possesses toxin-encoding genetic loci, but is commonly found in both intestinal and extra-intestinal infections. Membrane lipid rafts are composed of dynamic assemblies of cholesterol and sphingolipids, allowing bacteria to gain access to cells. However, the direct interaction between C. innocuum and lipid rafts that confers bacteria the ability to disrupt the intestinal barrier and induce pathogenesis remains unclear. In this study, we investigated the associations among nucleotide-binding oligomerization domain containing 2 (NOD2), lipid rafts, and cytotoxicity in C. innocuum-infected gut epithelial cells. Our results revealed that lipid rafts were involved in C. innocuum-induced NOD2 expression and nuclear factor (NF)-κB activation, triggering an inflammatory response. Reducing cholesterol by simvastatin significantly dampened C. innocuum-induced cell death, indicating that the C. innocuum-induced pathogenicity of cells was lipid raft-dependent. These results demonstrate that NOD2 mobilization into membrane rafts in response to C. innocuum-induced cytotoxicity results in aggravated pathogenicity.

Original languageEnglish
Article number2265048
JournalVirulence
Volume14
Issue number1
DOIs
StatePublished - 31 12 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • Clostridium innocuum
  • cholesterol
  • cytotoxicity
  • inflammation
  • lipid rafts

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