The gut’s hidden arsenal: A genomics-guided atlas of class II bacteriocins

Unmodified class II bacteriocins promise precision antimicrobials that spare bystander microbes. Zhang and colleagues introduce IIBacFinder, a genomics-guided pipeline that detects precursor and context genes with a curated pHMM library, infers leader-peptide cleavage, and triages candidates by meta-omics signals. The authors apply it across bacterial genomes, including an atlas of ∼280,000 human-gut genomes, and recover a vast reservoir of narrow-spectrum peptides and prioritize gut-resident candidates for synthesis. Of the 26 synthesized, 16 display activity in vitro, largely via membrane perturbation and with additive effects alongside vancomycin, while ex vivo assays show minimal compositional disruption of fecal communities compared with antibiotic controls. These results position unmodified class II bacteriocins as tractable, microbiome-sparing agents and illustrate how genome-scale mining coupled to meta-omics can bridge sequence to function in complex ecosystems.