Genome-guided discovery of antibiotic activity in <i>Streptomyces virginiae</i> THA-960 against multidrug resistant <i>Staphylococcus aureus</i>

The emergence of multidrug-resistant <i>Staphylococcus aureus</i> (MDR-<i>S. aureus</i>) demands innovative strategies to identify robust microbial producers of potent antibiotics. This study characterizes <i>Streptomyces virginiae</i> THA-960, a soil-derived actinomycete, as a producer of the known anti-MDR-<i>S. aureus</i> antibiotic. Phenotypic screening showed THA-960's efficacy against clinical MDR-<i>S. aureus</i> isolates, with MICs as low as 0.08 mg/mL, outperforming conventional antibiotic-producing <i>Streptomyces</i>. 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 <i>Streptomyces</i> genomes delineated <i>S. virginiae</i> 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 <i>Streptomyces</i> strains against antimicrobial resistance.