Evidence map›Paper›PMID 25824836›Full record

ArticleInfection and immunity2015

Inhibition of outer membrane proteases of the omptin family by aprotinin.

John R Brannon, David L Burk, Jean-Mathieu Leclerc, Jenny-Lee Thomassin, Andrea Portt, Albert M Berghuis, Samantha Gruenheid, Hervé Le Moual

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Review
  3. Protamine cleavage specificity of the avian pathogenFrontiers in veterinary science · 2024
    Article
  4. Article
  5. Article
  6. Article
  7. How the PhoP/PhoQ System Controls Virulence and MgMicrobiology and molecular biology reviews : MMBR · 2021
    Review
  8. Article
  9. Synergies with and Resistance to Membrane-Active Peptides.Antibiotics (Basel, Switzerland) · 2020
    Review
  10. Article
  11. Considerations and Caveats in Combating ESKAPE Pathogens against Nosocomial Infections.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020
    Review
  12. Article
  13. Article
  14. Review
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

John R BrannonDepartment of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
David L BurkDepartment of Biochemistry, McGill University, Montreal, Quebec, Canada.
Jean-Mathieu LeclercDepartment of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Jenny-Lee ThomassinDepartment of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Andrea PorttDepartment of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Albert M BerghuisDepartment of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Samantha GruenheidDepartment of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada.
Hervé Le MoualDepartment of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada Faculty of Dentistry, McGill University, Montreal, Quebec, Canada herve.le-moual@mcgill.ca.
McGill University · CA

Funding

Canadian Institutes of Health Research MOP-15551
6 · The paper itself

Abstract

Bacterial proteases are important virulence factors that inactivate host defense proteins and contribute to tissue destruction and bacterial dissemination. Outer membrane proteases of the omptin family, exemplified by Escherichia coli OmpT, are found in some Gram-negative bacteria. Omptins cleave a variety of substrates at the host-pathogen interface, including plasminogen and antimicrobial peptides. Multiple omptin substrates relevant to infection have been identified; nonetheless, an effective omptin inhibitor remains to be found. Here, we purified native CroP, the OmpT ortholog in the murine pathogen Citrobacter rodentium. Purified CroP was found to readily cleave both a synthetic fluorescence resonance energy transfer substrate and the murine cathelicidin-related antimicrobial peptide. In contrast, CroP was found to poorly activate plasminogen into active plasmin. Although classical protease inhibitors were ineffective against CroP activity, we found that the serine protease inhibitor aprotinin displays inhibitory potency in the micromolar range. Aprotinin was shown to act as a competitive inhibitor of CroP activity and to interfere with the cleavage of the murine cathelicidin-related antimicrobial peptide. Importantly, aprotinin was able to inhibit not only CroP but also Yersinia pestis Pla and, to a lesser extent, E. coli OmpT. We propose a structural model of the aprotinin-omptin complex in which Lys15 of aprotinin forms salt bridges with conserved negatively charged residues of the omptin active site.

Indexed as

Amino Acid SequenceAntimicrobial Cationic PeptidesAprotininBacterial Outer Membrane ProteinsCatalytic DomainCathelicidinsCitrobacter rodentiumEscherichia coli ProteinsFluorescence Resonance Energy TransferGene Expression Regulation, BacterialGene Expression Regulation, EnzymologicModels, MolecularPeptide HydrolasesProtein ConformationSerine ProteasesSerine Proteinase InhibitorsAntimicrobial Cationic PeptidesAprotininBacterial Outer Membrane ProteinsCathelicidinsEscherichia coli ProteinsompT protein, E coliPeptide HydrolasesSerine ProteasesSerine Proteinase Inhibitors

Identifiers

PMID25824836
PMCPMC4432765
OpenAlexW2114106011

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.