Blue-Light Photoactivation of Berberine-Gentamicin Combination: A Synergistic Strategy Against Staphylococcus aureus Acute Wound Infections

Background: Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge in managing acute wound infections due to its high resistance to conventional antibiotics. The persistence of these infections not only complicates treatment but also increases the likelihood of chronicity. This study investigates the potential of the blue-light photoactivated berberine-gentamicin (Ber-Gen) combination as a novel strategy to enhance bacterial inactivation and overcome antibiotic resistance in S. aureus. Methods: A clinical strain of MRSA isolated from a diabetic foot ulcer was used. The antibacterial activity of Ber and Gen was screened individually and in combination. The photodynamic activity of the Ber was assessed using a light-emitting diode (LED) system with blue light (420 nm), at 30 mW/cm2 (light doses of 9, 18, 27 J/cm2). The photodynamic activity of the Ber-Gen combination was evaluated after 6 h of incubation by the reduction of the culturability (colony forming units (CFU)/mL). Results: Ber significantly enhanced Gen activity, exhibiting a potentiating effect against MRSA. Blue-light activation of Ber (420 nm, 18 J/cm2) reduced its bactericidal concentration by 80-fold. The photodynamic activation of the Ber-Gen combination (420 nm, 10 min, 18 J/cm2) resulted in a ≈9-log CFU/mL reduction in S. aureus culturability, with a 2048-fold decrease in the bactericidal concentration of Gen. Conclusion: The dual approach of antimicrobial photodynamic inactivation combined with phytochemical-antibiotic combinations demonstrated a strong synergistic effect, effectively reducing S. aureus culturability and restoring the efficacy of Gen against MRSA. This approach shows promise as an innovative solution for managing antibiotic-resistant infections.