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Functional Assessment of Intestinal Permeability and Neutrophil Transepithelial Migration in Mice using a Standardized Intestinal Loop Model
Published on: February 11, 2021
The bacterial virulence factor lymphostatin compromises intestinal epithelial barrier function by modulating rho
Brian A Babbin1, Maiko Sasaki, Kirsten W Gerner-Schmidt
1Department of Pathology and Laboratory Medicine, Division of Digestive Diseases, Emory University, Atlanta, Georgia 30322, USA.
The American Journal of Pathology
|March 17, 2009
Summary
Citrobacter rodentium lymphostatin toxin disrupts intestinal barrier function. Its glucosyltransferase and protease motifs differentially affect epithelial junctions and Rho GTPase signaling, contributing to bacterial pathogenesis.
Area of Science:
- Microbiology
- Cell Biology
- Pathogenesis
Background:
- Citrobacter rodentium infection compromises intestinal epithelial barrier function.
- The bacterial toxin lymphostatin, encoded by lifA, possesses glucosyltransferase and protease motifs.
- Understanding the specific roles of these motifs in pathogenesis is crucial.
Purpose of the Study:
- To investigate the distinct effects of lymphostatin's glucosyltransferase and protease motifs on intestinal epithelial barrier integrity.
- To elucidate the underlying molecular mechanisms involving Rho GTPase signaling.
Main Methods:
- Generated in-frame mutations in C. rodentium lifA for glucosyltransferase (CrGlM21) and protease (CrPrM5).
- Infected epithelial monolayers and mice with wild-type and mutant C. rodentium strains.
- Analyzed epithelial barrier function, intercellular junction protein localization, and Rho GTPase activation.
Main Results:
- Wild-type C. rodentium disrupted epithelial barriers and junction proteins.
- CrGlM21 showed impaired barrier function effects and influenced tight junction proteins (ZO-1, occludin).
- CrPrM5 had reduced effects on adherens junction proteins (beta-catenin, E-cadherin) and failed to activate Rho signaling, while CrGlM21 lost Cdc42 suppression.
Conclusions:
- Lymphostatin is a virulence factor disrupting intestinal epithelial barriers.
- The toxin's motifs differentially modulate Rho GTPase activity, impacting barrier function.
- Targeting lymphostatin's enzymatic activities could be a therapeutic strategy against C. rodentium infections.
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