Overcoming MRSA biofilms and resistance: The re-emergence of phage therapy and synergistic approaches

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major cause of healthcare-associated and community-acquired infections worldwide, with its multifaceted resistance mechanisms, such as β-lactam resistance, robust biofilm formation reliant on polysaccharide intercellular adhesin and extracellular DNA, efflux pump overexpression, and target-site modifications leading to reduced susceptibility to last-line agents like linezolid and daptomycin, contributing to high recurrence rates and therapeutic failures. The emergence of vancomycin-resistant strains (VRSA) intensifies these challenges in the context of the global antimicrobial resistance crisis. Literature review of studies from recent years highlights the potent efficacy of bacteriophage-based approaches, including multi-phage cocktails, synergistic antibiotic combinations, endolysins, and CRISPR-engineered phages, in targeting planktonic cells, disrupting biofilms, and eradicating resistant subpopulations. Encouraging results from ongoing trials and compassionate-use cases underscore the safety and effectiveness of these strategies in managing chronic infections. Ultimately, phage therapy presents a precise, adaptable, and microbiota-sparing alternative that holds transformative potential for treating multidrug-resistant S. aureus infections, warranting accelerated clinical development and regulatory advancement despite persisting challenges in standardization.