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Actinomyces Produces Defensin-Like Bacteriocins (Actifensins) with a Highly Degenerate Structure and Broad Antimicrobial Activity
Sugrue, Ivan O’Connor, Paula M. Hill, Colin Stanton, Catherine Ross, R. Paul
Sugrue, Ivan
O’Connor, Paula M.
Hill, Colin
Stanton, Catherine
Ross, R. Paul
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2020-01-29
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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.