Calpain mediates epithelial cell microvillar effacement by enterohemorrhagic Escherichia coli

A member of the attaching and effacing (AE) family of pathogens, enterohemorrhagic Escherichia coli (EHEC) induces dramatic changes to the intestinal cell cytoskeleton, including effacement of microvilli. Effacement by the related pathogen enteropathogenic E. coli (EPEC) requires the activity of the...

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Main Authors: YuShuan eLai, Kathleen eRiley, Andrew eCai, John M Leong, Ira M. Herman
Format: Article
Language:English
Published: Frontiers Media S.A. 2011-11-01
Series:Frontiers in Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fmicb.2011.00222/full
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author YuShuan eLai
Kathleen eRiley
Andrew eCai
Andrew eCai
John M Leong
Ira M. Herman
author_facet YuShuan eLai
Kathleen eRiley
Andrew eCai
Andrew eCai
John M Leong
Ira M. Herman
author_sort YuShuan eLai
collection DOAJ
description A member of the attaching and effacing (AE) family of pathogens, enterohemorrhagic Escherichia coli (EHEC) induces dramatic changes to the intestinal cell cytoskeleton, including effacement of microvilli. Effacement by the related pathogen enteropathogenic E. coli (EPEC) requires the activity of the Ca+2-dependent host protease, calpain, which participates in a variety of cellular processes, including cell adhesion and motility. We found that EHEC infection results in an increase in epithelial (CaCo-2a) cell calpain activity and that EHEC-induced microvillar effacement was blocked by ectopic expression of calpastatin, an endogenous calpain inhibitor, or by pretreatment of intestinal cells with a cell-penetrating version of calpastatin. In addition, ezrin, a known calpain substrate that links the plasma membrane to axial actin filaments in microvilli, was cleaved in a calpain-dependent manner during EHEC infection and lost from its normal locale within microvilli. Calpain may be a central conduit through which EHEC and other AE pathogens induce enterocyte cytoskeletal remodeling and exert their pathogenic effects.
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spelling doaj.art-e7dd9cbc8a164f8e99c0afe69bd7a8212022-12-22T00:08:57ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2011-11-01210.3389/fmicb.2011.0022213003Calpain mediates epithelial cell microvillar effacement by enterohemorrhagic Escherichia coliYuShuan eLai0Kathleen eRiley1Andrew eCai2Andrew eCai3John M Leong4Ira M. Herman5University of Massachusetts Medical SchoolTufts UniversityUniversity of Massachusetts Medical SchoolTufts UniversityUniversity of Massachusetts Medical SchoolTufts UniversityA member of the attaching and effacing (AE) family of pathogens, enterohemorrhagic Escherichia coli (EHEC) induces dramatic changes to the intestinal cell cytoskeleton, including effacement of microvilli. Effacement by the related pathogen enteropathogenic E. coli (EPEC) requires the activity of the Ca+2-dependent host protease, calpain, which participates in a variety of cellular processes, including cell adhesion and motility. We found that EHEC infection results in an increase in epithelial (CaCo-2a) cell calpain activity and that EHEC-induced microvillar effacement was blocked by ectopic expression of calpastatin, an endogenous calpain inhibitor, or by pretreatment of intestinal cells with a cell-penetrating version of calpastatin. In addition, ezrin, a known calpain substrate that links the plasma membrane to axial actin filaments in microvilli, was cleaved in a calpain-dependent manner during EHEC infection and lost from its normal locale within microvilli. Calpain may be a central conduit through which EHEC and other AE pathogens induce enterocyte cytoskeletal remodeling and exert their pathogenic effects.http://journal.frontiersin.org/Journal/10.3389/fmicb.2011.00222/fullMicrovilliattaching and effacing (AE) lesionCaCo-2CalpastatcalpastatinEzrin
spellingShingle YuShuan eLai
Kathleen eRiley
Andrew eCai
Andrew eCai
John M Leong
Ira M. Herman
Calpain mediates epithelial cell microvillar effacement by enterohemorrhagic Escherichia coli
Frontiers in Microbiology
Microvilli
attaching and effacing (AE) lesion
CaCo-2
Calpastat
calpastatin
Ezrin
title Calpain mediates epithelial cell microvillar effacement by enterohemorrhagic Escherichia coli
title_full Calpain mediates epithelial cell microvillar effacement by enterohemorrhagic Escherichia coli
title_fullStr Calpain mediates epithelial cell microvillar effacement by enterohemorrhagic Escherichia coli
title_full_unstemmed Calpain mediates epithelial cell microvillar effacement by enterohemorrhagic Escherichia coli
title_short Calpain mediates epithelial cell microvillar effacement by enterohemorrhagic Escherichia coli
title_sort calpain mediates epithelial cell microvillar effacement by enterohemorrhagic escherichia coli
topic Microvilli
attaching and effacing (AE) lesion
CaCo-2
Calpastat
calpastatin
Ezrin
url http://journal.frontiersin.org/Journal/10.3389/fmicb.2011.00222/full
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