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Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
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Targeting the Dynamic Susceptibility Window: Time-Sensitive Photodynamic Synergy With Antibiotics Against

Isabella S Gonçalves1,2, Jennifer M Soares2,3, Vanderlei S Bagnato2,3

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|February 27, 2026
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Summary

Curcumin-mediated photodynamic inactivation (PDI) effectively kills bacteria and enhances antibiotic action against Streptococcus pneumoniae and Streptococcus pyogenes. Optimal timing of PDI application is crucial for maximizing synergistic effects with antibiotics.

Keywords:
Streptococcus pneumoniaeStreptococcus pyogenesantibioticantimicrobial resistancecurcuminphotodynamic therapy

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Area of Science:

  • Microbiology and Infectious Diseases
  • Photochemistry and Photobiology
  • Pharmacology and Drug Discovery

Background:

  • Streptococcus pneumoniae and Streptococcus pyogenes are significant human pathogens.
  • Antibiotic resistance necessitates novel therapeutic strategies.
  • Curcumin exhibits antimicrobial properties and can act as a photosensitizer.

Purpose of the Study:

  • To evaluate curcumin-mediated photodynamic inactivation (PDI) against S. pneumoniae and S. pyogenes.
  • To assess the synergistic effect of curcumin-PDI with antibiotics (amoxicillin, ceftriaxone, erythromycin).
  • To determine the optimal timing for PDI application to enhance antibiotic efficacy.

Main Methods:

  • Minimum inhibitory concentrations (MICs) of antibiotics were determined.
  • Curcumin-PDI was applied to bacterial cultures followed by LED irradiation.
  • Bacterial viability was assessed using colony-forming units (CFUs) over time.
  • Combinatorial effects of antibiotics and PDI were evaluated at subinhibitory concentrations.

Main Results:

  • Curcumin-PDI alone achieved significant bacterial reduction (>3-log).
  • Combined therapy markedly enhanced bactericidal activity, especially with β-lactams (up to 2.8-log greater reduction).
  • Multiple PDI treatments reduced MICs up to 128-fold, indicating potentiation.
  • Synergistic effects were time-dependent, highlighting a dynamic susceptibility window.

Conclusions:

  • Curcumin-PDI is an effective antimicrobial agent against S. pneumoniae and S. pyogenes.
  • The timing of PDI application is critical for maximizing synergistic effects with antibiotics.
  • This approach offers a promising strategy for combating antibiotic-resistant bacterial infections.