Video: Evolution under vancomycin selection drives divergent collateral sensitivity patterns in Staphylococcus aureus

Antibiotic treatment can influence bacterial evolution, altering the effectiveness of subsequent therapies by inducing collateral resistance or sensitivity. Our study reveals that evolution toward vancomycin-intermediate resistance in the pathogen Staphylococcus aureus proceeds through at least two distinct evolutionary pathways: one characterized by alterations in cell wall metabolism and another by changes in global stress response. These adaptive trajectories result in contrasting collateral sensitivities to first-line antibiotics. By introducing the Collateral Response Score, we assess the uncertainty in these outcomes, providing a probabilistic framework to evaluate how past antibiotic exposure shapes future treatment responses. Further validation studies are needed; however, we believe that improved forecasting of pathogen evolution can enhance antibiotic stewardship, inform therapeutic decisions, and ultimately improve patient outcomes.