Molecular Mechanisms and Emerging Strategies to Combat Antimicrobial Resistance: A Review

Abstract

AMR develops as a result of microbial evolution under selective pressure imposed by antimicrobial use. Although antimicrobial resistance occurs in bacteria, fungi, viruses, and parasites, this review specifically focuses on bacterial antimicrobial resistance resulting from antibiotic exposure. The mechanisms, causes, and emerging strategies related to bacterial antibiotic resistance are comprehensively analyzed. We investigate the molecular and physiological processes, such as chromosomal mutations, horizontal gene transfer, drug uptake limitation, antimicrobial target modification, enzymatic drug inactivation, active efflux systems, and biofilmassociated tolerance that underlie the development of resistance. The review highlights the distinctions between Gram-positive and Gram-negative bacteria while delving deeper into intrinsic and acquired resistance mechanisms within a unified molecular framework. Important clinical, environmental, and ecological factors that accelerate the emergence and spread of resistance are examined in addition to mechanistic discoveries. Heavy metal co-selection, wastewater and environmental contamination, improper use of antibiotics in healthcare and agriculture, poor infection control procedures, and the growing role of microplastics as resistance gene vectors are some of these. A One Health viewpoint addresses transmission dynamics in clinical, community, agricultural, and environmental settings. Lastly, we critically assess existing and emerging techniques to combat AMR, including computational methods, combination and adjuvant medicines, unique and alternative therapeutic platforms, enhanced diagnostics, genomic surveillance, and antimicrobial stewardship. This review identifies key areas for research, policy, and concerted international action to maintain antibiotic efficacy by combining molecular understanding with practical issues and future directions.