Actinomyces produces defensin-like bacteriocins (Actifensins) with a highly degenerate structure and broad antimicrobial activity

dc.contributor.authorSugrue, Ivan
dc.contributor.authorO'Connor, Paula M.
dc.contributor.authorHill, Colin
dc.contributor.authorStanton, Catherine
dc.contributor.authorRoss, R. Paul
dc.contributor.funderTeagascen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderJoint Programming Initiative A healthy diet for a healthy lifeen
dc.date.accessioned2020-03-31T11:18:17Z
dc.date.available2020-03-31T11:18:17Z
dc.date.issued2020-01-29
dc.date.updated2020-03-31T11:04:10Z
dc.description.abstractWe identified a strain of Actinomyces ruminicola which produces a potent bacteriocin with activity against a broad range of Gram-positive bacteria, many of which are pathogenic to animals and humans. The bacteriocin was purified and found to have a mass of 4,091 ± 1 Da with a sequence of GFGCNLITSNPYQCSNHCKSVGYRGGYCKLRTVCTCY containing three disulfide bridges. Surprisingly, near relatives of actifensin were found to be a series of related eukaryotic defensins displaying greater than 50% identity to the bacteriocin. A pangenomic screen further revealed that production of actifensin-related bacteriocins is a common trait within the genus, with 47 being encoded in 161 genomes. Furthermore, these bacteriocins displayed a remarkable level of diversity with a mean amino acid identity of only 52% between strains/species. This level of redundancy suggests that this new class of bacteriocins may provide a very broad structural basis on which to deliver and design new broad-spectrum antimicrobials for treatment of animal and human infections. IMPORTANCE: Bacteriocins (ribosomally produced antimicrobial peptides) are potential alternatives to current antimicrobials given the global challenge of antimicrobial resistance. We identified a novel bacteriocin from Actinomyces ruminicola with no previously characterized antimicrobial activity. Using publicly available genomic data, we found a highly conserved yet divergent family of previously unidentified homologous peptide sequences within the genus Actinomyces with striking similarity to eukaryotic defensins. These actifensins may provide a potent line of antimicrobial defense/offense, and the machinery to produce them could be used for the design of new antimicrobials given the degeneracy that exists naturally in their structure.en
dc.description.sponsorshipTeagasc (Teagasc Walsh Fellowship); Joint Programming Initiative (JPI Food Processing for Health Longlife Project)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide00529-19en
dc.identifier.citationSugrue, I., O'Connor, P. M.; Hill, C., Stanton, C., and Ross, R. P. (2020) 'Actinomyces Produces Defensin-Like Bacteriocins (Actifensins) with a Highly Degenerate Structure and Broad Antimicrobial Activity', Journal of Bacteriology, 202 (4), e00529-19, (15 pp). doi: 10.1128/JB.00529-19en
dc.identifier.doi10.1128/JB.00529-19en
dc.identifier.endpage15en
dc.identifier.issn1098-5530
dc.identifier.issued4en
dc.identifier.journaltitleJournal of Bacteriologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9795
dc.identifier.volume202en
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.relation.urihttps://jb.asm.org/content/202/4/e00529-19
dc.rights© 2020 Sugrue et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectActifensinen
dc.subjectActinomycesen
dc.subjectAntimicrobial peptideen
dc.subjectBacteriocinen
dc.subjectDefensinen
dc.titleActinomyces produces defensin-like bacteriocins (Actifensins) with a highly degenerate structure and broad antimicrobial activityen
dc.typeArticle (peer-reviewed)en
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