Mechanistic basis of multidrug resistance: Current status, challenges, and potential solutions

The emergence of drug-resistant microbes is a significant global health concern, driven by the inappropriate and excessive use of antibiotics across sectors worldwide, which has led to the development of antimicrobial resistance (AMR). The rise of multidrug-resistant organisms has posed substantial challenges for healthcare systems globally, with the history of AMR tracing back to the discovery of penicillin. The improper use of antibiotics in human and animal healthcare, along with their application in agriculture, contributes to the spread of resistance genes, leading to a "Silent Pandemic" that could surpass other causes of death by 2050. AMR complicates the effective treatment of infections, affecting both human and animal populations. Bacteria can withstand the effects of antibiotics by employing several strategies, such as forming biofilms and undergoing enzymatic changes. If not addressed, the lack of effective antibiotics could jeopardize common medical procedures and potentially result in millions of deaths each year. The economic impact of AMR is expected to impose enormous financial burdens and projected losses in the trillions of dollars for healthcare systems and agriculture. Adopting a One Health strategy that considers human, animal, and environmental aspects is crucial for effectively tackling AMR. This includes enhancing surveillance systems, advocating stewardship programs, and allocating funding to research and development to discover new antibiotic alternatives. To address AMR and ensure the effectiveness of antibiotics for future generations, it is essential to prioritize raising public awareness, providing education, and fostering international collaboration. • In bacterial systems, genetic adaptation, efflux pump overexpression, enzymatic inactivation, and target site alteration are some of the mechanisms that lead to antimicrobial resistance (AMR). • New approaches that show great promise for fighting resistant diseases include CRISPR-Cas gene editing, antimicrobial peptides, bacteriophage therapy, and nano-antibiotics. • Drug target identification and antibacterial discovery are being accelerated by the integration of omics technologies, computational biology, and artificial intelligence. • Synthetic biology and genomic mining are making it possible to create new antibacterial chemicals from both natural and artificial sources. • Multidisciplinary strategies integrating microbiology, nanotechnology, bioinformatics, international surveillance, and policy coordination are needed to combat AMR.