Fructose metabolic heterogeneity drives vancomycin tolerance in clonal Staphylococcus aureus biofilms.

Vancomycin induces heterogeneous upregulation of fructose metabolism genes in Staphylococcus aureus biofilms, creating metabolically active and reduced subpopulations that influence antibiotic tolerance.

• Why it matters: Understanding how metabolic heterogeneity contributes to biofilm antibiotic recalcitrance is crucial for developing effective treatments, especially since biofilms are a major obstacle in clinical infection control.
• What they did: Single-cell RNA sequencing was used to analyze S. aureus ATCC 12600 biofilms' response to vancomycin, revealing spatially segregated subpopulations with distinct metabolic states and survival strategies.
• The result: Active cells with increased fructose consumption enhance cell wall thickening, promoting vancomycin tolerance, while metabolically reduced cells activate oxidative stress repair, and elevated systemic fructose levels in diabetic mice worsen pulmonary infections, highlighting clinical relevance.