Prophage and metabolic determinants of Staphylococcus aureus survival to vancomycin identified via TraDIS screening.

Disruption of 52 genes, including prophage-associated loci, is linked to loss of S. aureus survival under vancomycin at its minimum inhibitory concentration.

• Why it matters: Understanding genetic factors behind vancomycin tolerance is crucial because treatment failure often occurs without known resistance genes, indicating other survival mechanisms are involved.
• What they did: Using transposon-directed insertion-site sequencing on a MRSA ST398 library, researchers identified genes associated with survival, and confirmed that disrupting selected loci impaired growth under vancomycin in a USA300 background.
• The result: Findings suggest that vancomycin tolerance depends on broad physiological processes, including metabolism, stress responses, and prophage functions, emphasizing the importance of cellular physiology in antibiotic survival strategies.