ArticlePloS one2013
Identification of a novel zinc metalloprotease through a global analysis of Clostridium difficile extracellular proteins.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- CenIR, an essential BlaIR-family regulatory system inJournal of bacteriology · 2026Article
- Design and Synthesis of Phosphonoproline-Proline Bioisosteric Mimetics of Proline Dimers: Pseudopeptide Constructs as Potential Inhibitors of the Zn-Metalloprotease PPEP‑1 Associated withACS medicinal chemistry letters · 2026Article
- CenIR, an essential BlaIR-family regulatory system inbioRxiv : the preprint server for biology · 2026Article
- Bacterial zinc metalloproteases as facilitators of pathogenic success: a review.Archives of microbiology · 2026Review
- Zinc Glycinate Alleviates Necrotic Enteritis Infection in Broiler Chickens.Animals : an open access journal from MDPI · 2025Article
- Immunization Strategies Against Clostridioides difficile.Advances in experimental medicine and biology · 2024Review
- Review
- Towards Development of a Non-ToxigenicPharmaceutics · 2022Article
- Structural and Biochemical Analysis of the Furan Aldehyde Reductase YugJ fromInternational journal of molecular sciences · 2022Article
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- Phylogenetic analysis of the bacterial Pro-Pro-endopeptidase domain reveals a diverse family including secreted and membrane anchored proteins.Current research in microbial sciences · 2021Review
- A Bioluminescent Sensor for Rapid Detection of PPEP-1, aSensors (Basel, Switzerland) · 2021Article
- Identification and Validation of Reference Genes inFrontiers in microbiology · 2021Article
- Leptospirosis is an invasive infectious and systemic inflammatory disease.Biomedical journal · 2020Review
- Molecular determinants of the mechanism and substrate specificity ofThe Journal of biological chemistry · 2019Article
- Impact of CodY protein on metabolism, sporulation and virulence in Clostridioides difficile ribotype 027.PloS one · 2019Article
- Discovery of a new Pro-Pro endopeptidase, PPEP-2, provides mechanistic insights into the differences in substrate specificity within the PPEP family.The Journal of biological chemistry · 2018Article
- Cyclic-di-GMP regulation of virulence in bacterial pathogens.Wiley interdisciplinary reviews. RNA · 2018Review
- TargetingFrontiers in microbiology · 2018Review
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.