Antibiotic Mechanisms and Resistance: Molecular Insights and Therapeutic Strategies

Antibiotic resistance is a critical global health threat, already causing over 1.27 million deaths annually and projected to exceed 10 million by 2050. This crisis is compounded by stagnation in novel antibiotic discovery, highlighting the need for mechanism–based innovation. Here, we provide an integrative framework linking antibiotic mechanisms of action, bacterial resistance pathways, and emerging therapeutic strategies. Antibiotics are systematically categorized by their molecular targets, cell wall synthesis, membrane integrity, nucleic acid replication, protein synthesis, and metabolic pathways, while resistance mechanisms are outlined in parallel, including enzymatic degradation, target modification, efflux, and permeability barriers. We further highlight novel approaches such as structure–guided drug design, synergistic combinations, nanoparticle delivery, and artificial intelligence–driven discovery. Precision medicine and microbiome modulation are also emphasized as next–generation interventions. By bridging molecular mechanisms with translational strategies, this review outlines opportunities to guide antibiotic innovation and advance precision therapies against the escalating threat of antimicrobial resistance.