The Inactivating Antibiotic Resistance Genes Regulate Antimicrobial Resistance Evolutionary Trajectories

Antimicrobial resistance (AMR) represents one of the most challenging global health challenges of our time. While extensive research has focused on resistance mechanisms and their spread, a critical knowledge gap persists in our understanding of inactivating antibiotic resistance genes (inactivating ARGs) and their regulatory role in shaping AMR evolution. This oversimplification limits our understanding of AMR dynamics and potentially misdirects risk mitigation and control strategies. Our study addresses this critical gap by revealing a previously unrecognized time-dependent regulatory mechanism by which inactivating ARGs shape the evolutionary development of AMR under antibiotic stress.