Document Detail


Potent diarrheagenic mechanism mediated by the cooperative action of three enteropathogenic Escherichia coli-injected effector proteins.
MedLine Citation:
PMID:  16446436     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Enteropathogenic Escherichia coli (EPEC) induces a severe watery diarrhea responsible for several hundred thousand infant deaths each year by a process correlated with the loss (effacement) of absorptive microvilli. Effacement is linked to the locus of enterocyte effacement pathogenicity island that encodes an "injection system," "effector" proteins, and the Intimin outer membrane protein. Here, we reveal that effacement (i) is a two-step process, (ii) requires the cooperative action of three injected effectors (Map, EspF, and Tir) as well as Intimin, and (iii) leads to the retention, not release (into the extracellular milieu), of the detached microvillar material. We also discover that EPEC rapidly inactivates the sodium-d-glucose cotransporter (SGLT-1) by multiple mechanisms. Indeed, the finding that one mechanism occurs more rapidly than microvilli effacement provides a plausible explanation for the rapid onset of severe watery diarrhea, given the crucial role of SGLT-1 in the daily uptake of approximately 6 liters of fluids from the normal intestine. The importance of SGLT-1 in the disease process is supported by severe EPEC diarrheal cases being refractory to oral rehydration therapy (dependent on SGLT-1 function). Moreover, the identification of effector activities that alter microvilli structure and SGLT-1 function provides new tools for studying the underlying regulatory processes.
Authors:
Paul Dean; Marc Maresca; Stephanie Schüller; Alan D Phillips; Brendan Kenny
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-01-30
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  103     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-09     Completed Date:  2006-03-23     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1876-81     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adhesins, Bacterial / metabolism
Caco-2 Cells
Diarrhea / genetics,  metabolism*
Escherichia coli / physiology*,  ultrastructure
Escherichia coli Proteins / genetics,  metabolism*
Humans
Kinetics
Microscopy, Electron, Scanning
Receptors, Cell Surface / metabolism
Sodium-Glucose Transporter 1 / genetics,  metabolism
Time Factors
Grant Support
ID/Acronym/Agency:
G9721484//Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Adhesins, Bacterial; 0/Escherichia coli Proteins; 0/Receptors, Cell Surface; 0/Sodium-Glucose Transporter 1
Comments/Corrections

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