Document Detail


Functional association between the Helicobacter pylori virulence factors VacA and CagA.
MedLine Citation:
PMID:  18201978     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Helicobacter pylori virulence factors CagA and VacA are implicated in the development of gastroduodenal diseases. Most strains possessing CagA also possess the more virulent vacuolating form of VacA. This study assessed the significance of possession of both virulence factors in terms of their effect on gastric epithelial cells, using a set of minimally passaged, isogenic VacA, CagA and CagE mutants in H. pylori strains 60190 and 84-183. The cagA and cagE mutants were found to significantly increase VacA-induced vacuolation of epithelial cells, and the vacA mutants significantly increased CagA-induced cellular elongations, compared with wild-type strains, indicating that CagA reduces vacuolation and VacA reduces hummingbird formation. Although epithelial cells incubated with the wild-type H. pylori strains may display both vacuolation and hummingbird formation, it was found that (i) hummingbird length was significantly reduced in vacuolated cells compared with those without vacuolation; (ii) the number of vacuoles was significantly reduced in vacuolated cells with hummingbird formation compared with those without hummingbirds; and (iii) cells displaying extensive vacuolation did not subsequently form hummingbirds and vice versa. VacA did not affect the phosphorylation of CagA. These data show that VacA and CagA downregulate each other's effects on epithelial cells, potentially allowing H. pylori interaction with cells whilst avoiding excessive cellular damage.
Authors:
Richard H Argent; Rachael J Thomas; Darren P Letley; Michael G Rittig; Kim R Hardie; John C Atherton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medical microbiology     Volume:  57     ISSN:  0022-2615     ISO Abbreviation:  J. Med. Microbiol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-18     Completed Date:  2008-04-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0224131     Medline TA:  J Med Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  145-50     Citation Subset:  IM    
Affiliation:
Institute of Infection, Immunity and Inflammation, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK. richard.argent@nottingham.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Antigens, Bacterial / genetics,  physiology*
Bacterial Proteins / genetics,  physiology*
Cell Line
Cell Shape
Cell Survival
Epithelial Cells / cytology,  metabolism,  microbiology*
Gene Deletion
Helicobacter pylori / genetics,  pathogenicity*
Interleukin-8 / metabolism
Neutral Red / metabolism
Vacuoles / microbiology
Virulence Factors / physiology*
Grant Support
ID/Acronym/Agency:
//Cancer Research UK; //Medical Research Council
Chemical
Reg. No./Substance:
0/Antigens, Bacterial; 0/Bacterial Proteins; 0/Interleukin-8; 0/PicB protein, Helicobacter pylori; 0/VacA protein, Helicobacter pylori; 0/Virulence Factors; 0/cagA protein, Helicobacter pylori; 553-24-2/Neutral Red

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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