Clostridium difficile toxin CDT hijacks microtubule organization and reroutes vesicle traffic to increase pathogen adherence

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Item Type:	Article
Title:	Clostridium difficile toxin CDT hijacks microtubule organization and reroutes vesicle traffic to increase pathogen adherence
Creators Name:	Schwan, C., Kruppke, A.S., Nölke, T., Schumacher, L., Koch-Nolte, F., Kudryashev, M., Stahlberg, H. and Aktories, K.
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, Biological Transport, Caco-2 Cells, Calcium Signaling, Clostridioides difficile, Endoplasmic Reticulum, Enterotoxins, Fibronectins, Microtubules
Source:	Proceedings of the National Academy of Sciences of the United States of America
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Volume:	111
Number:	6
Page Range:	2313-2318
Date:	11 February 2014
Official Publication:	https://doi.org/10.1073/pnas.1311589111
PubMed:	View item in PubMed

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