Clostridium difficile toxin CDT hijacks microtubule organization and reroutes vesicle traffic to increase pathogen adherence.
Details
Serval ID
serval:BIB_35E082E739F3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Clostridium difficile toxin CDT hijacks microtubule organization and reroutes vesicle traffic to increase pathogen adherence.
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
11/02/2014
Peer-reviewed
Oui
Volume
111
Number
6
Pages
2313-2318
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis by the actions of Rho-glucosylating toxins A and B. Recently identified hypervirulent strains, which are associated with increased morbidity and mortality, additionally produce the actin-ADP-ribosylating toxin C. difficile transferase (CDT). CDT depolymerizes actin, causes formation of microtubule-based protrusions, and increases pathogen adherence. Here we show that CDT-induced protrusions allow vesicle traffic and contain endoplasmic reticulum tubules, connected to microtubules via the calcium sensor Stim1. The toxin reroutes Rab11-positive vesicles containing fibronectin, which is involved in bacterial adherence, from basolateral to the apical membrane sides in a microtubule- and Stim1-dependent manner. The data yield a model of C. difficile adherence regulated by actin depolymerization, microtubule restructuring, subsequent Stim1-dependent Ca(2+) signaling, vesicle rerouting, and secretion of ECM proteins to increase bacterial adherence.
Keywords
Bacterial Adhesion, Bacterial Toxins/toxicity, Biological Transport, Caco-2 Cells, Calcium Signaling, Clostridioides difficile/metabolism, Clostridioides difficile/pathogenicity, Endoplasmic Reticulum/drug effects, Enterotoxins/toxicity, Fibronectins/metabolism, Humans, Microtubules/drug effects
Pubmed
Web of science
Open Access
Yes
Create date
09/06/2023 16:03
Last modification date
20/07/2023 6:57