Jacob Scott, professor of radiation oncology at Case Western Reserve University School of Medicine, recently was published in the Proceedings of the National Academy of Sciences (PNAS) for his research related to bacterial evolution.
The article, titled “Evolution under vancomycin selection drives divergent collateral sensitivity patterns in Staphylococcus aureus,” investigates collateral drug responses of Staphylococcus aureus bacteremia, which causes serious infections, and its resistance through two main genetic pathways.
The research findings suggest a probabilistic approach to antimicrobial therapy, advocating for rapid genomic diagnostics alongside susceptibility testing to better anticipate and respond to evolutionary changes.
About the study
Staphylococcus aureus bacteremia is typically treated empirically with vancomycin, with therapy later tailored based on susceptibility results. However, these tests occur before vancomycin exposure and do not account for adaptation during empiric treatment that can alter S. aureus’ susceptibility to first-line drugs. To investigate collateral drug responses, the team experimentally evolved 18 methicillin-susceptible S. aureus populations under increasing vancomycin concentrations until they achieved intermediate resistance.
Genomic sequencing revealed two distinct adaptive pathways characterized by mutations in the WalKR regulon, affecting cell wall metabolism, or rpsU, impacting translational stress responses. These pathways correlated with divergent collateral sensitivity profiles to first-line antibiotics. By developing a Collateral Response Score, researchers quantified the probability and magnitude of these responses, demonstrating that evolutionary dynamics critically influence resistance outcomes.
A new PNAS study shows that Staphylococcus aureus can take different routes to resist vancomycin, a common frontline antibiotic. Each route leaves the bug with a very different pattern of weaknesses to other drugs—meaning the treatment that works after resistance emerges depends on how the bacteria evolved. To capture this, the researchers created a Collateral Response Score, a way to estimate the odds that past antibiotic use will shape future drug effectiveness.
The big idea: by combining fast genetic testing with smarter forecasting, doctors could stay one step ahead of bacterial evolution and make antibiotic choices that keep working longer.
