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Identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins
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Cafardi, Valeria, Biagini, Massimiliano, Martinelli, Manuele, Leuzzi, Rosanna, Rubino, Jeffrey T., Cantini, Francesca, Norais, Nathalie, Scarselli, Maria, Serruto, Davide and Unnikrishnan, Meera (2013) Identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins. PLoS One, Volume 8 (Number 11). Article number e81306. doi:10.1371/journal.pone.0081306
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Official URL: http://dx.doi.org/10.1371/journal.pone.0081306
Abstract
Clostridium difficile is a major cause of infectious diarrhea worldwide. Although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. Also, apart from the toxins, proteins exported by C. difficile into the extracellular milieu have been poorly studied. In order to identify novel extracellular factors of C. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and R20291, using liquid chromatography-tandem mass spectrometry. The majority of the proteins identified were non-canonical extracellular proteins. These could be largely classified into proteins associated to the cell wall (including CWPs and extracellular hydrolases), transporters and flagellar proteins. Seven unknown hypothetical proteins were also identified. One of these proteins, CD630_28300, shared sequence similarity with the anthrax lethal factor, a known zinc metallopeptidase. We demonstrated that CD630_28300 (named Zmp1) binds zinc and is able to cleave fibronectin and fibrinogen in vitro in a zinc-dependent manner. Using site-directed mutagenesis, we identified residues important in zinc binding and enzymatic activity. Furthermore, we demonstrated that Zmp1 destabilizes the fibronectin network produced by human fibroblasts. Thus, by analyzing the exoproteome of C. difficile, we identified a novel extracellular metalloprotease that may be important in key steps of clostridial pathogenesis.
| Item Type: | Journal Article | ||||
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| Subjects: | R Medicine > R Medicine (General) | ||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection Faculty of Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Clostridium difficile , Metalloproteinases, Zinc | ||||
| Journal or Publication Title: | PLoS One | ||||
| Publisher: | Public Library of Science | ||||
| ISSN: | 1932-6203 | ||||
| Official Date: | 2013 | ||||
| Dates: |
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| Date of first compliant deposit: | 26 December 2015 | ||||
| Volume: | Volume 8 | ||||
| Number: | Number 11 | ||||
| Page Range: | Article number e81306 | ||||
| DOI: | 10.1371/journal.pone.0081306 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Open Access |
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