Antimicrobial resistance (AMR) is a significant global health challenge that threatens the effectiveness of antibiotics and other antimicrobial agents. Here, we examined the molecular mechanisms that contribute to bacterial resistance, including alterations at target sites, enzymatic inactivation, efflux pump overexpression, and biofilm formation. Key resistance determinants, such as blaCTX-M-15, blaNDM-1, mecA, and erm genes, mediate enzymatic degradation and target modification, thereby diminishing antibiotic potency. Clinically significant pathogens, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecium, exemplify a broad spectrum of resistance and frequently acquire these traits through horizontal gene transfer (HGT), facilitated by plasmids, integrons, and transposons. The propensity for biofilm formation further augments bacterial persistence by impeding antimicrobial penetration and fostering intra-community genetic exchanges. The clinical ramifications of AMR are profound, contributing to elevated morbidity and mortality, extended hospitalization, and increased rates of therapeutic failure, all of which exert significant strain on the healthcare system. The economic consequences are equally severe, with escalating healthcare expenditures and substantial projected losses to the global gross domestic product (GDP). Addressing these challenges necessitates the adoption of advanced approaches, including genomic surveillance, antimicrobial stewardship, novel inhibitors targeting resistance pathways, immuno-antibiotics, and bacteriophage therapy. This review underscores the need to integrate molecular diagnostics and a One Health perspective to monitor and contain resistance across human, animal, and environmental reservoirs. A comprehensive understanding of the molecular and epidemiological aspects of AMR is essential for driving advancements in diagnostics, therapeutics, and policies, thereby ensuring global health protection.
Citation: Sabiha Nusrat, Mansur Aliyu, Fatema Tuz Zohora. Mechanisms of antimicrobial resistance: From genetic evolution to clinical manifestations[J]. AIMS Microbiology, 2025, 11(4): 1007-1034. doi: 10.3934/microbiol.2025045
Antimicrobial resistance (AMR) is a significant global health challenge that threatens the effectiveness of antibiotics and other antimicrobial agents. Here, we examined the molecular mechanisms that contribute to bacterial resistance, including alterations at target sites, enzymatic inactivation, efflux pump overexpression, and biofilm formation. Key resistance determinants, such as blaCTX-M-15, blaNDM-1, mecA, and erm genes, mediate enzymatic degradation and target modification, thereby diminishing antibiotic potency. Clinically significant pathogens, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecium, exemplify a broad spectrum of resistance and frequently acquire these traits through horizontal gene transfer (HGT), facilitated by plasmids, integrons, and transposons. The propensity for biofilm formation further augments bacterial persistence by impeding antimicrobial penetration and fostering intra-community genetic exchanges. The clinical ramifications of AMR are profound, contributing to elevated morbidity and mortality, extended hospitalization, and increased rates of therapeutic failure, all of which exert significant strain on the healthcare system. The economic consequences are equally severe, with escalating healthcare expenditures and substantial projected losses to the global gross domestic product (GDP). Addressing these challenges necessitates the adoption of advanced approaches, including genomic surveillance, antimicrobial stewardship, novel inhibitors targeting resistance pathways, immuno-antibiotics, and bacteriophage therapy. This review underscores the need to integrate molecular diagnostics and a One Health perspective to monitor and contain resistance across human, animal, and environmental reservoirs. A comprehensive understanding of the molecular and epidemiological aspects of AMR is essential for driving advancements in diagnostics, therapeutics, and policies, thereby ensuring global health protection.
Antimicrobial resistance
World health organization
Horizontal gene transfer
Resistance-nodulation-division
Major facilitator superfamily
Small multidrug resistance
ATP-binding cassette
Extended-spectrum β-Lactamase
Penicillin-binding protein 2a
Methicillin-resistant
Whole genome sequencing
Centers for disease control and prevention
Deoxyribonucleic acid
Ribonucleic acid
Polymerase chain reaction
Coronavirus disease 2019
Reverse transcriptase
Multidrug resistance
Minimum inhibitory concentration
Minimum bactericidal concentration
National health service
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Figures(3) / Tables(3)
Sabiha Nusrat, Mansur Aliyu, Fatema Tuz Zohora. Mechanisms of antimicrobial resistance: From genetic evolution to clinical manifestations[J]. AIMS Microbiology, 2025, 11(4): 1007-1034. doi: 10.3934/microbiol.2025045
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