Staphylococcus aureus Biofilms: Challenges and Advances in Bacteriophage Therapy

Staphylococcus aureus biofilms are a significant cause of persistent and chronic infections, especially on indwelling medical devices. They exhibit mechanisms to resist antibiotics and host immune defenses. The emergence of multidrug-resistant strains like methicillin-resistant S. aureus has intensified the need for alternative therapeutic approaches. Bacteriophage therapy, utilizing viruses that specifically infect and kill bacteria, has regained interest as a potential strategy to combat S. aureus biofilms due to its specificity and ability to disrupt biofilm structure. However, several challenges limit the clinical application of phage therapy against biofilms, including limited penetration of the biofilm matrix, narrow host range, development of phage-resistant bacterial subpopulations, decreased metabolic activity of bacteria within biofilms, and quorum sensing (QS)–mediated defense mechanisms. This review discusses the molecular basis of S. aureus biofilm formation and persistence, summarizes the current advances and limitations of phage therapy targeting biofilms, and explores future perspectives and counterstrategies such as phage engineering, combination therapies, and QS inhibition to enhance therapeutic efficacy. Understanding and overcoming these challenges are critical for advancing phage therapy as a viable treatment option for biofilm-associated S. aureus infections.