PLoS Pathogens | |
Clostridium difficile Toxin CDT Induces Formation of Microtubule-Based Protrusions and Increases Adherence of Bacteria | |
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
【 预 览 】
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