ArticlePLoS pathogens2019
Ecotin, a microbial inhibitor of serine proteases, blocks multiple complement dependent and independent microbicidal activities of human serum.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- MucD regulates alginate biosynthesis through the proteolytic control of AlgX and AlgK in Pseudomonas aeruginosa.PLoS biology · 2026Article
- Strain-specific variation in the complement resistome ofInfection and immunity · 2025Article
- The living medicine inside us:Gut microbes reports · 2025Article
- Metabolic Reprogramming ofJournal of proteome research · 2024Article
- The bacterial serine protease inhibitor ecotin inhibits neutrophil elastase enzymatic activity in cystic fibrosis sputa.Heliyon · 2024Article
- Transcriptional biomarker discovery toward building a load stress reporting system for engineered Escherichia coli strains.Biotechnology and bioengineering · 2024Article
- The potential of bacterial anti-phagocytic proteins in suppressing the clearance of extracellular vesicles mediated by host phagocytosis.Frontiers in immunology · 2024Review
- Subversion of the Complement System by Pseudomonas aeruginosa.Journal of bacteriology · 2023Review
- Shotgun Proteomics Analysis, Functional Networks, and Peptide Biomarkers for Seafood-Originating Biogenic-Amine-Producing Bacteria.International journal of molecular sciences · 2023Article
- Review
- Article
- Ecotin: A versatile protease inhibitor of bacteria and eukaryotes.Frontiers in microbiology · 2023Review
- Pathogenicity and virulence ofVirulence · 2022Review
- Arg236 in human chymotrypsin B2 (CTRB2) is a key determinant of high enzyme activity, trypsinogen degradation capacity, and protection against pancreatitis.Biochimica et biophysica acta. Proteins and proteomics · 2022Article
- Synergy of protease-binding sites within the ecotin homodimer is crucial for inhibition of MASP enzymes and for blocking lectin pathway activation.The Journal of biological chemistry · 2022Article
- Directed Evolution-Driven Increase of Structural Plasticity Is a Prerequisite for Binding the Complement Lectin Pathway Blocking MASP-Inhibitor Peptides.ACS chemical biology · 2022Article
- Sequence preference and scaffolding requirement for the inhibition of human neutrophil elastase by ecotin peptide.Protein science : a publication of the Protein Society · 2022Article
- Lipoproteome screening of the Lyme disease agent identifies inhibitors of antibody-mediated complement killing.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Molecular Mechanisms Involved in Pseudomonas aeruginosa Bacteremia.Advances in experimental medicine and biology · 2022Review
- Characterization of Differentially Abundant Proteins AmongFrontiers in cellular and infection microbiology · 2022Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ecotin is a serine protease inhibitor produced by hundreds of microbial species, including pathogens. Here we show, that ecotin orthologs from Escherichia coli, Yersinia pestis, Pseudomonas aeruginosa and Leishmania major are potent inhibitors of MASP-1 and MASP-2, the two key activator proteases of the complement lectin pathway. Factor D is the key activator protease of another complement activation route, the alternative pathway. We show that ecotin inhibits MASP-3, which is the sole factor D activator in resting human blood. In pathway-specific ELISA tests, we found that all ecotin orthologs are potent lectin pathway inhibitors, and at high concentration, they block the alternative pathway as well. In flow cytometry experiments, we compared the extent of complement-mediated opsonization and lysis of wild-type and ecotin-knockout variants of two E. coli strains carrying different surface lipopolysaccharides. We show, that endogenous ecotin provides significant protections against these microbicidal activities for both bacteria. By using pathway specific complement inhibitors, we detected classical-, lectin- and alternative pathway-driven complement attack from normal serum, with the relative contributions of the activation routes depending on the lipopolysaccharide type. Moreover, in cell proliferation experiments we observed an additional, complement-unrelated antimicrobial activity exerted by heat-inactivated serum. While ecotin-knockout cells are highly vulnerable to these activities, endogenous ecotin of wild-type bacteria provides complete protection against the lectin pathway-related and the complement-unrelated attack, and partial protection against the alternative pathway-related damage. In all, ecotin emerges as a potent, versatile self-defense tool that blocks multiple antimicrobial activities of the serum. These findings suggest that ecotin might be a relevant antimicrobial drug target.
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