Document Detail

Cholesterol depletion reduces entry of Campylobacter jejuni cytolethal distending toxin and attenuates intoxication of host cells.
MedLine Citation:
PMID:  21730089     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-07-05
Journal Detail:
Title:  Infection and immunity     Volume:  79     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-17     Completed Date:  2011-10-21     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3563-75     Citation Subset:  IM    
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.:
GENBANK/JF520784;  JF682840
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MeSH Terms
Bacterial Toxins / genetics,  metabolism*
CHO Cells
Campylobacter jejuni / metabolism,  pathogenicity*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Membrane / metabolism
Cholesterol / metabolism*,  pharmacology
Flow Cytometry
Membrane Microdomains / metabolism*
Mice, Inbred BALB C
Molecular Sequence Data
Virulence Factors / metabolism
beta-Cyclodextrins / pharmacology
Reg. No./Substance:
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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