Methicillin Resistant Staphylococcus aureus: Molecular Mechanisms Underlying Drug Resistance Development and Novel Strategies to Combat

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Abstract: Antimicrobial resistance (AMR) represents a major threat to global health. Infection caused by Methicillin-resistant Staphylococcus aureus (MRSA) is one of the well-recognized global public health problem globally. In some regions, as many as 90% of S. aureus infections are reported to be MRSA, which cannot be treated with standard antibiotics. WHO reports indicated that MRSA is circulating in every province worldwide, significantly increasing the risk of death by 64% compared to drug-sensitive forms of the infection which is attributed to its antibiotic resistance. The emergence and spread of antibiotic-resistant MRSA strains have contributed to its increased prevalence in both healthcare and community settings. The resistance of S. aureus to methicillin is due to expression of penicillin-binding protein 2a (PBP2a), which renders it impervious to the action of β-lactam antibiotics including methicillin. The other is through the production of beta-lactamases. Although the treatment options for MRSA are limited, there are promising alternatives to antibiotics to combat the infections. Innovative therapeutic strategies with wide range of activity and modes of action are yet to be explored. The review highlights the global challenges posed by MRSA, elucidates the mechanisms underlying its resistance development, and explores mitigation strategies. Furthermore, it focuses on alternative therapies such as bacteriophages, immunotherapy, nanobiotics, and antimicrobial peptides, emphasizing their synergistic effects and efficacy against MRSA. By examining these alternative approaches, this review provides insights into the potential strategies for tackling MRSA infections and combatting the escalating threat of AMR. Ultimately, a multifaceted approach encompassing both conventional and novel interventions is imperative to mitigate the impact of MRSA and ensure a sustainable future for global healthcare. Keywords: MRSA, AMR, resistome, phage therapy, nanoparticles, antimicrobial peptides, lytic

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