Cholesterol depletion reduces entry of Campylobacter jejuni cytolethal distending toxin and attenuates intoxication of host cells

Chia Der Lin, Cheng Kuo Lai, Yu Hsin Lin, Jer Tsong Hsieh, Yu Ting Sing, Yun Chieh Chang, Kai Chuan Chen, Wen Ching Wang, Hong Lin Su, Chih Ho Lai

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Campylobacter jejuni is a common cause of pediatric diarrhea worldwide. Cytolethal distending toxin, produced by Campylobacter jejuni, is a putative virulence factor that induces cell cycle arrest and apoptosis in eukaryotic cells. Cellular cholesterol, a major component of lipid rafts, has a pivotal role in regulating signaling transduction and protein trafficking as well as pathogen internalization. In this study, we demonstrated that cell intoxication by Campylobacter jejuni cytolethal distending toxin is through the association of cytolethal distending toxin subunits and membrane cholesterol-rich microdomains. Cytolethal distending toxin subunits cofractionated with detergent-resistant membranes, while the distribution reduced upon the depletion of cholesterol, suggesting that cytolethal distending toxin subunits are associated with lipid rafts. The disruption of cholesterol using methyl-β-cyclodextrin not only reduced the binding activity of cytolethal distending toxin subunits on the cell membrane but also impaired their delivery and attenuated toxin-induced cell cycle arrest. Accordingly, cell intoxication by cytolethal distending toxin was restored by cholesterol replenishment. These findings suggest that membrane cholesterol plays a critical role in the Campylobacter jejuni cytolethal distending toxin-induced pathogenesis of host cells.

Original languageEnglish (US)
Pages (from-to)3563-3575
Number of pages13
JournalInfection and immunity
Volume79
Issue number9
DOIs
StatePublished - Sep 1 2011

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Lin, C. D., Lai, C. K., Lin, Y. H., Hsieh, J. T., Sing, Y. T., Chang, Y. C., Chen, K. C., Wang, W. C., Su, H. L., & Lai, C. H. (2011). Cholesterol depletion reduces entry of Campylobacter jejuni cytolethal distending toxin and attenuates intoxication of host cells. Infection and immunity, 79(9), 3563-3575. https://doi.org/10.1128/IAI.05175-11