Circumnavigating Antibiotic Mechanisms of Action and Resistance Research

Antibiotics have revolutionized human health by significantly reducing morbidity and mortality associated with bacterial infections. Antibiotics exert bactericidal or bacteriostatic effects through inhibition of cell wall synthesis and disruption of cell membrane integrity, inhibition of protein, nucleic acid synthesis, and other metabolic pathways. Despite their remarkable success since the mid-20th century, antimicrobial resistance (AMR) has emerged as a major global health concern, undermining current treatments and complicating infection management. Key drivers of AMR include the overuse and misuse of antibiotics in clinical settings as well as bacterial adaptations such as genetic mutations and horizontal gene transfer. Mechanistically, these changes can lead to enzymatic inactivation of antibiotics, modification of drug targets, changes in permeability, and active efflux of antimicrobial agents. As resistance rises, antibiotic discovery and development have lagged, creating an urgent need for novel therapeutic strategies and chemical scaffolds. This review examines the antibiotic mechanisms and antibiotic evasion strategies, highlighting genetic and omics approaches used to identify high-priority targets for future drug discovery.