| Cholesterol depletion reduces entry of Campylobacter jejuni cytolethal distending toxin and attenuates intoxication of host cells. | |
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MedLine Citation:
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PMID: 21730089 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-07-05 |
Journal Detail:
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Title: Infection and immunity Volume: 79 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-17 Completed Date: 2011-10-21 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 3563-75 Citation Subset: IM |
Affiliation:
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School of Medicine and Graduate Institute of Basic Medical Science, China Medical University, No. 91 Hsueh-Shih Road, Taichung, 40402 Taiwan. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/JF520784; JF682840 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bacterial Toxins / genetics, metabolism* CHO Cells Campylobacter jejuni / metabolism, pathogenicity* Cell Cycle / drug effects Cell Line, Tumor Cell Membrane / metabolism Cholesterol / metabolism*, pharmacology Cricetinae Cricetulus Flow Cytometry Humans Membrane Microdomains / metabolism* Mice Mice, Inbred BALB C Molecular Sequence Data Virulence Factors / metabolism beta-Cyclodextrins / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Bacterial Toxins; 0/Virulence Factors; 0/beta-Cyclodextrins; 0/cytolethal distending toxin; 0/methyl-beta-cyclodextrin; 57-88-5/Cholesterol |
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