Involvement of cholesterol in Campylobacter jejuni cytolethal distending toxin-induced pathogenesis

Future Microbiol. 2015;10(4):489-501. doi: 10.2217/fmb.14.119.

Abstract

Aim: The aim of this study was to investigate whether cholesterol plays a pivotal role in cytolethal distending toxin (CDT) mediated pathogenic effects in hosts.

Materials & methods: The molecular mechanisms underlying cholesterol sequestering conferred resistance to CDT-induced DNA double-strand breaks (DSBs) and cell cycle arrest were investigated. Histopathological analysis was conducted for evaluating CDT-induced intestinal inflammation in mouse.

Results: CDT actions were attenuated by treatment of cells with methyl-β-cyclodextrin (MβCD). Severe intestinal inflammation induced by CDT treatment was observed in high-cholesterol diet-fed mice, but not in normal diet-fed mice, indicating that cholesterol is essential for CDT intoxication.

Conclusion: Our findings demonstrate a molecular link between Campylobacter jejuni CDT and cholesterol, which is crucial to facilitate CDT-induced pathogenesis in hosts.

Keywords: Campylobacter jejuni; DNA double-strand breaks; cell cycle; cholesterol; cytolethal distending toxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / toxicity*
  • Campylobacter Infections / pathology
  • Campylobacter jejuni / metabolism*
  • Cholesterol / metabolism*
  • Diet / methods
  • Disease Models, Animal
  • Histocytochemistry
  • Host-Pathogen Interactions*
  • Intestines / pathology
  • Mice

Substances

  • Bacterial Toxins
  • cytolethal distending toxin
  • Cholesterol