Genome-guided discovery of antibiotic activity in Streptomyces virginiae THA-960 against multidrug resistant...

The emergence of multidrug-resistant Staphylococcus aureus (MDR-S. aureus) demands innovative strategies to identify robust microbial producers of potent antibiotics. This study characterizes Streptomyces virginiae THA-960, a soil-derived actinomycete, as a producer of the known anti-MDR-S. aureus antibiotic. Phenotypic screening showed THA-960's efficacy against clinical MDR-S. aureus isolates, with MICs as low as 0.08 mg/mL, outperforming conventional antibiotic-producing Streptomyces. Time-kill assays and SEM confirmed rapid bactericidal action via cell wall disruption. Complete genome sequencing revealed a rich biosynthetic potential, housing 31 specialized metabolite gene clusters. Phylogenomic analysis of 521 Streptomyces genomes delineated S. virginiae into distinct groups and showed that the amycomicin biosynthetic gene cluster is conserved within a specific taxonomic group, providing a genomic roadmap for targeted strain selection. Crucially, Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Qtof-MS) analysis detected a metabolite feature putatively assigned as amycomicin in THA-960. This integrated multi-omics study provides a phylogenomic framework for the targeted exploitation of Streptomyces strains against antimicrobial resistance.