The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Clostridium difficile Toxin CDT Induces Formation of Microtubule-Based Protrusions and Increases Adherence of Bacteria
Open accessAbstract
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 microm) 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.
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Cites
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Cited by
Lawley, T. D., Clare, S., Walker, A. W., Stares, M. D., Connor, T. R., Raisen, C., Goulding, D., Rad, R., Schreiber, F., Brandt, C., et al. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002995 · Cited by 540
Carey-Ann, B. D., & Carroll, K. C. (2013) · Clinical Microbiology Reviews · doi:10.1128/cmr.00016-13 · Cited by 423
Clostridium difficile binary toxin CDT: Mechanism, epidemiology, and potential clinical importance
Gerding, D. N., Johnson, S., Rupnik, M., & Aktories, K. (2014) · Gut Microbes · doi:10.4161/gmic.26854 · Cited by 416
Self-citationThe role of toxins in Clostridium difficile infection
Chandrasekaran, R., & Lacy, D. B. (2017) · FEMS Microbiology Reviews · doi:10.1093/femsre/fux048 · Cited by 353
Clostridium difficile Infection: A Worldwide Disease
Burke, K. E., & Lamont, J. T. (2014) · Gut and Liver · doi:10.5009/gnl.2014.8.1.1 · Cited by 274
Metadata
- Authors
- Schwan, C., Stecher, B., Tzivelekidis, T., van Ham, M., Rohde, M., Hardt, W.-D., Wehland, J., & Aktories, K.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-10-16
- Volume
- 5
- Issue
- 10
- Pages
- e1000626
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- OpenAlex
- W2077103365
- Cited by
- 337
- References
- 63
- FWCI
- 17.38
- Type
- journal article
- Language
- en
- Open access
- gold
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- Schwan, C., Stecher, B., Tzivelekidis, T., van Ham, M., Rohde, M., Hardt, W.-D., Wehland, J., & Aktories, K. (2009). Clostridium difficile Toxin CDT Induces Formation of Microtubule-Based Protrusions and Increases Adherence of Bacteria. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1000626
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