How New Peptides Combat MRSA: Mechanisms, Resistance, and Translational Challenges : A Narrative Review

Background: Methicillin-resistant Staphylococcus aureus (MRSA) remains a significant global health threat due to its multidrug resistance, biofilm formation, and high viru-lence, which collectively limit the efficacy of conventional antibiotics and drive the need for alternative therapeutic approaches. Objectives: To review the current progress in antimicrobial peptides (AMPs) as therapeutic candidates against MRSA, focusing on mechanisms of action, resistance circumvention, formulation strategies, translational challenges, and future perspectives. Methods: Narrative review of recent studies on AMPs targeting MRSA, including peptide engineering, chemical modifications, and de-livery approaches to enhance stability, potency, and specificity. Results: AMPs exert multifaceted effects such as membrane disruption, inhibition of intracellular targets, interference with biofilm formation, and modulation of host immune responses. Their pleiotropic mechanisms reduce the likelihood of resistance development, and engi-neering strategies including cyclization, stapling, and conjugation with lipids or nano-particles improve pharmacokinetics and target specificity. Conclusions: AMPs represent promising therapeutic alternatives against MRSA. Understanding their mechanisms, optimizing peptide design, and developing effective delivery strategies are essential for clinical translation in the post-antibiotic era.