Document Detail


Cytolethal distending toxin family members are differentially affected by alterations in host glycans and membrane cholesterol.
MedLine Citation:
PMID:  20385557     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytolethal distending toxins (CDTs) are tripartite protein exotoxins produced by a diverse group of pathogenic Gram-negative bacteria. Based on their ability to induce DNA damage, cell cycle arrest, and apoptosis of cultured cells, CDTs are proposed to enhance virulence by blocking cellular division and/or directly killing epithelial and immune cells. Despite the widespread distribution of CDTs among several important human pathogens, our understanding of how these toxins interact with host cells is limited. Here we demonstrate that CDTs from Haemophilus ducreyi, Aggregatibacter actinomycetemcomitans, Escherichia coli, and Campylobacter jejuni differ in their abilities to intoxicate host cells with defined defects in host factors previously implicated in CDT binding, including glycoproteins, and glycosphingolipids. The absence of cell surface sialic acid sensitized cells to intoxication by three of the four CDTs tested. Surprisingly, fucosylated N-linked glycans and glycolipids, previously implicated in CDT-host interactions, were not required for intoxication by any of the CDTs tested. Finally, altering host-cellular cholesterol, also previously implicated in CDT binding, affected intoxication by only a subset of CDTs tested. The findings presented here provide insight into the molecular and cellular basis of CDT-host interactions.
Authors:
Aria Eshraghi; Francisco J Maldonado-Arocho; Amandeep Gargi; Marissa M Cardwell; Michael G Prouty; Steven R Blanke; Kenneth A Bradley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-04-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-06-29     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18199-207     Citation Subset:  IM    
Affiliation:
Department of Microbiology, University of California, Los Angeles, California 90095, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacterial Toxins / chemistry*,  genetics*
CHO Cells
Campylobacter jejuni / metabolism
Cholesterol / chemistry*,  metabolism
Cricetinae
Cricetulus
DNA Damage
Escherichia coli / metabolism
Glycolipids / chemistry
Gram-Negative Bacteria / metabolism
Haemophilus ducreyi / metabolism
HeLa Cells
Humans
Mice
NIH 3T3 Cells
Polysaccharides / chemistry*
Protein Binding
Grant Support
ID/Acronym/Agency:
AI59095/AI/NIAID NIH HHS; F31AI061837/AI/NIAID NIH HHS; T32DE007296/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Bacterial Toxins; 0/Glycolipids; 0/Polysaccharides; 0/cytolethal distending toxin; 57-88-5/Cholesterol
Comments/Corrections

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