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    Actinomyces Produces Defensin-Like Bacteriocins (Actifensins) with a Highly Degenerate Structure and Broad Antimicrobial Activity

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    Author
    Sugrue, Ivan
    O’Connor, Paula M.
    Hill, Colin
    Stanton, Catherine
    Ross, R. Paul
    Keyword
    Actinomyces
    bacteriocin
    defensin
    antimicrobial peptide
    actifensin
    Date
    2020-01-29
    
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    URI
    http://hdl.handle.net/11019/2658
    Citation
    Sugrue I, O’Connor PM, Hill C, Stanton C, Ross RP. 2020. Actinomyces produces defensin-like bacteriocins (actifensins) with a highly degenerate structure and broad antimicrobial activity. J Bacteriol 202:e00529-19. https://doi.org/10.1128/JB.00529-19
    Abstract
    We 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.
    Funder
    Teagasc Walsh Fellowship Programme; JPI; Science Foundation Ireland
    Grant Number
    SFI/12/RC/2273
    ae974a485f413a2113503eed53cd6c53
    https://doi.org/10.1128/JB.00529-19
    Scopus Count
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    Food Biosciences

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