Clostridium difficile Toxin CDT Induces Formation of Microtubule-Based Protrusions and Increases Adherence of Bacteria

PLoS Pathogens

Manfred Rohde¹  Bärbel Stecher¹  Jürgen Wehland²  Wolf-Dietrich Hardt²  Carsten Schwan³  Marco van Ham³  Klaus Aktories⁴  Tina Tzivelekidis⁴ 

[1] Fakultät Biologie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany;Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany;Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany;Institut für Mikrobiologie, Eidgenössische Technische Hochschule, ETH Zürich, Zürich, Switzerland

关键词: Toxins;    Microtubules;    Clostridium difficile;    Caco-2 cells;    Actins;    Actin filaments;    Clostridium;    Tubulins;   

DOI  :  10.1371/journal.ppat.1000626

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis by production of the Rho GTPase-glucosylating toxins A and B. Recently emerging hypervirulent Clostridium difficile strains additionally produce the binary ADP-ribosyltransferase toxin CDT (Clostridium difficile transferase), which ADP-ribosylates actin and inhibits actin polymerization. Thus far, the role of CDT as a virulence factor is not understood. Here we report by using time-lapse- and immunofluorescence microscopy that CDT and other binary actin-ADP-ribosylating toxins, including Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin, induce redistribution of microtubules and formation of long (up to >150 µm) microtubule-based protrusions at the surface of intestinal epithelial cells. The toxins increase the length of decoration of microtubule plus-ends by EB1/3, CLIP-170 and CLIP-115 proteins and cause redistribution of the capture proteins CLASP2 and ACF7 from microtubules at the cell cortex into the cell interior. The CDT-induced microtubule protrusions form a dense meshwork at the cell surface, which wrap and embed bacterial cells, thereby largely increasing the adherence of Clostridia. The study describes a novel type of microtubule structure caused by less efficient microtubule capture and offers a new perspective for the pathogenetic role of CDT and other binary actin-ADP-ribosylating toxins in host–pathogen interactions.

【 授权许可】

CC BY