Multi-locus pairing expands the functional repertoire of two-peptide bacteriocins

In streptococci, two-peptide bacteriocins can form functional antimicrobial pairs across distinct chromosomal loci, yielding 54 active peptide combinations from 47 peptides.

• Why it matters: The field has treated peptide pairing as confined to a single biosynthetic locus, but genomic and functional evidence suggests a broader modular pairing logic that could expand antimicrobial diversity.
• What they did: Comparative genomics identified frequent co-occurrence of putative two-peptide bacteriocins at separate loci; pairwise testing of 47 peptides by cell-free protein synthesis found 54 enhanced combinations, and split-luciferase assays in Streptococcus mitis C22 showed sequence-dependent peptide association.
• The result: In Streptococcus mitis C22, four dispersed bacteriocin loci are coordinately expressed during exponential growth, and in a bacteriocin-free S. mitis background, cross-cell components increase competitiveness in co-culture with S. pneumoniae.

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