Metabolism as a driver of antibiotic resistance

Antibiotic resistance remains one of the most pressing challenges in modern microbiology. Decades of research have focused on identifying resistance genes and molecular mechanisms in opportunistic pathogens. Yet bacterial survival under antibiotic stress is often shaped by broader physiological processes that are not always considered within the conventional frameworks associated with antibiotic resistance. In this perspective, I argue that bacterial metabolism plays a broader and more integrative role in shaping antibiotic resistance than is often appreciated. I discuss how metabolic networks and core housekeeping genes may serve as underlying drivers of bacterial survival and adaptation during antibiotic exposure. Integrating metabolic context into resistance research may reveal new evolutionary insights and highlight previously unrecognized vulnerabilities in bacterial physiology. Indeed, viewing antibiotic resistance through the lens of metabolism may ultimately help guide the development of more effective, ‘metabolism-aware’ antimicrobial strategies.