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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Schüller, Stephanie Phillips, Alan D. Dean, Paul Maresca, Marc Kenny, Brendan |
| Description | Author Affiliation: Dean P ( Institute for Cell and Molecular Biosciences, Medical School, University of Newcastle, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom.); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Diarrhea Metabolism Escherichia Coli Proteins Escherichia Coli Physiology Adhesins, Bacterial Caco-2 Cells Genetics Ultrastructure Kinetics Microscopy, Electron, Scanning Receptors, Cell Surface Sodium-Glucose Transporter 1 Time Factors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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