Campylobacter jejuni Cytolethal Distending Toxin C Exploits Lipid Rafts to Mitigate Helicobacter pylori-Induced Pathogenesis

Jia Yin Yeh, Hwai Jeng Lin, Chia Jung Kuo, Chun Lung Feng, Chia Huei Chou, Chia Der Lin, Hui Yu Wu, Chen Yi Li, Cheng Hsun Chiu, Chih Ho Lai

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcer, and gastrointestinal adenocarcinoma. Two major cytotoxins, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), interact closely with lipid rafts, contributing to H. pylori-associated disease progression. The Campylobacter jejuni cytolethal distending toxin consists of three subunits: CdtA, CdtB, and CdtC. Among them, CdtA and CdtC bind to membrane lipid rafts, which is crucial for CdtB entry into cells. In this study, we employed recombinant CdtC (rCdtC) to antagonize the functions of H. pylori cytotoxin in cells. Our results showed that rCdtC alleviates cell vacuolation induced by H. pylori VacA. Furthermore, rCdtC reduces H. pylori CagA translocation, which decreases nuclear factor kappa-B activation and interleukin-8 production, resulting in the mitigation of gastric epithelial cell inflammation. These results reveal that CdtC hijacks cholesterol to compete for H. pylori cytotoxin actions via lipid rafts, ameliorating H. pylori-induced pathogenesis.

Original languageEnglish
Article number617419
JournalFrontiers in Cell and Developmental Biology
Volume8
DOIs
Publication statusPublished - Feb 23 2021

Keywords

  • cytolethal distending toxin
  • cytotoxin-associated gene A
  • Helicobacter pylori
  • lipid rafts
  • vacuolating cytotoxin A

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Campylobacter jejuni Cytolethal Distending Toxin C Exploits Lipid Rafts to Mitigate Helicobacter pylori-Induced Pathogenesis'. Together they form a unique fingerprint.

Cite this