Cited by 116Gut microbiota and healthBacteriophages and microbial interactionsGenomics and Phylogenetic Studies

A Novel Extracellular Metallopeptidase Domain Shared by Animal Host-Associated Mutualistic and Pathogenic Microbes

Open access
Nakjang, Sirintra, Ndeh, Didier A., Wipat, Anil, Bolam, David N., Hirt, Robert P.·2012·PLoS ONE

Abstract

The mucosal microbiota is recognised as an important factor for our health, with many disease states linked to imbalances in the normal community structure. Hence, there is considerable interest in identifying the molecular basis of human-microbe interactions. In this work we investigated the capacity of microbes to thrive on mucosal surfaces, either as mutualists, commensals or pathogens, using comparative genomics to identify co-occurring molecular traits. We identified a novel domain we named M60-like/PF13402 (new Pfam entry PF13402), which was detected mainly among proteins from animal host mucosa-associated prokaryotic and eukaryotic microbes ranging from mutualists to pathogens. Lateral gene transfers between distantly related microbes explained their shared M60-like/PF13402 domain. The novel domain is characterised by a zinc-metallopeptidase-like motif and is distantly related to known viral enhancin zinc-metallopeptidases. Signal peptides and/or cell surface anchoring features were detected in most microbial M60-like/PF13402 domain-containing proteins, indicating that these proteins target an extracellular substrate. A significant subset of these putative peptidases was further characterised by the presence of associated domains belonging to carbohydrate-binding module family 5/12, 32 and 51 and other glycan-binding domains, suggesting that these novel proteases are targeted to complex glycoproteins such as mucins. An in vitro mucinase assay demonstrated degradation of mammalian mucins by a recombinant form of an M60-like/PF13402-containing protein from the gut mutualist Bacteroides thetaiotaomicron. This study reveals that M60-like domains are peptidases targeting host glycoproteins. These peptidases likely play an important role in successful colonisation of both vertebrate mucosal surfaces and the invertebrate digestive tract by both mutualistic and pathogenic microbes. Moreover, 141 entries across various peptidase families described in the MEROPS database were also identified with carbohydrate-binding modules defining a new functional context for these glycan-binding domains and providing opportunities to engineer proteases targeting specific glycoproteins for both biomedical and industrial applications.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0030287

Cites

91 of 91 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The M60-like protease family cleaves the mucin glycoprotein backbone in a manner dependent on the presence of specific glycan sidechain structures.

    “the M60-like protease family cleaves the mucin glycoprotein backbone in a manner that is dependent on the presence of specific glycan sidechain structures.125,126”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

3 of the 94 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. [8]Cone RA 2005 Mucus. Mestecky J Lamm ME McGhee JR Bienenstock J Mayer L Mucosal Immunology. 3rd ed Burlington Elsevier 49 72
  2. [21]Carlton JM Malik SB Sullivan SA Sicheritz-Ponten T Tang P 2010 The genome of Trichomonas vaginalis. Clark CG Johnson PJ Adam RD Anaerobic Parasitic Protozoa: Genomics and Molecular Biology: Caister Academic Press 45 77
  3. [62]Hobbs MM Seña AC Swygard H Schwekke JR 2007 Trichomonas vaginalis and trichomononisasis. Holmes K Sparling S Stamm W Piot P Wasserheit J Sexually transmitted diseases. 4th ed McGraw-Hill Professional 771 794

Cited by

Sorted by citations

Authors
Nakjang, S., Ndeh, D. A., Wipat, A., Bolam, D. N., & Hirt, R. P.
Affiliations
Newcastle University (GB)
Corresponding author
  • Nakjang, Sirintra
  • Ndeh, Didier A.
  • Wipat, Anil
  • Bolam, David N.
  • Hirt, Robert P.
Venue
PLoS ONE
Published
2012-01-27
Volume
7
Issue
1
Pages
e30287
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2015392436
Cited by
116
References
94
Citations by year
2026: 10 · 2025: 4 · 2024: 12 · 2023: 5 · 2022: 12 · 2021: 7 · 2020: 15 · 2019: 14 · 2018: 5 · 2017: 5 · 2016: 7 · 2015: 3 · 2014: 7 · 2013: 7 · 2012: 3
FWCI
2.57
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders
  • Wellcome Trust
  • Newcastle University
  • Commonwealth Scholarship Commission
  • Department for International Development
  • Fakultet Medicinskih Nauka, Univerziteta U Kragujevcu
  • Biotechnology and Biological Sciences Research Council (BB/F014163/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
extracellular peptidases, mucin degradation, mucin, host-microbe interactions, mucosal microbiota, horizontal gene transfer, carbohydrate-binding module, Bacteroides thetaiotaomicron, host colonization, signal peptide
MeSH terms
Adaptation, Biological, Amino Acid Sequence, Animals, Base Sequence, Digestive System, Humans, Invertebrates, Molecular Sequence Data, Symbiosis, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Metalloproteases, Host-Pathogen Interactions

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review