Targeting the Dynamic Susceptibility Window: Time-Sensitive Photodynamic Synergy With Antibiotics Against Streptococcus spp.

OBJECTIVE

Evaluated the antimicrobial efficacy of curcumin-mediated photodynamic inactivation (PDI) against both sensitive and resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes, as well as its potential to enhance antibiotic effects (amoxicillin, ceftriaxone, erythromycin).

METHODOLOGY: The minimum inhibitory concentrations of antibiotics A, B, and C were evaluated in S. pneumoniae and S. pyogenes strains using serial microdilution. Additionally, the photodynamic action of curcumin as a photosensitizer was examined in multiwell plates, which were then irradiated with a 450-nm LED. The effect of the combination over time was determined by colony-forming units per milliliter, using the determined subinhibitory parameters of antibiotics and PDI.

RESULTS

PDI alone significantly reduced bacterial viability, achieving over 3-log reductions at optimal conditions (2.5 µM curcumin, 6.4 J/cm2). When combined with antibiotics, PDI markedly enhanced bactericidal activity, particularly with β-lactams, producing up to 2.8 log greater reductions than antibiotics alone. Notably, three consecutive PDI treatments led to substantial MIC reductions, up to 128-fold for S. pyogenes. We identified that the synergistic effect of curcumin-PDI is highly time-dependent, revealing a dynamic susceptibility window that can be exploited for enhanced antibiotic action. These results support curcumin-PDI as both an antimicrobial tool and a sensitizer agent that enhances antibiotic efficacy.

CONCLUSION

The study highlights that optimal timing of PDI application is key to maximizing its synergistic effects with antibiotics, revealing that PDI is most effective when applied during specific stages of bacterial response to antibiotic stress, potentially redefining adjuvant treatment strategies.