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Photo-activated porphyrin in combination with antibiotics: therapies against Staphylococci
Sana S Dastgheyb1, David M Eckmann, Russell J Composto
1Department of Orthopaedic Surgery, Jefferson Medical College, 1015 Walnut St., Suite 501, Philadelphia, PA 19107, United States.
Abstract:
Staphylococcal infections have become difficult to treat due to antibiotic insensitivity and resistance. Antimicrobial combination therapies may minimize acquisition of resistance and photodynamic therapy is an attractive candidate for these combinations. In this manuscript, we explore combined use of antibiotics and meso-tetra (4-aminophenyl) porphine (TAPP), a cationic porphyrin, for treatment of Staphylococcus aureus contamination. We characterize the antimicrobial activity of photoactivated TAPP and show that activity is largely lost in the presence of a radical scavenger. Importantly, TAPP can be reactivated with continued, albeit attenuated, antibacterial activity. We then show that the antimicrobial activity of illuminated TAPP is additive with chloramphenicol and tobramycin for S. aureus and Escherichia coli, and synergistic for MRSA and Staphylococcus epidermidis. Chloramphenicol+methylene blue, another photosensitizer, also show additivity against S. aureus. In contrast, ceftriaxone and vancomycin do not strongly augment the low level effects of TAPP against S. aureus. Eukaryotic cells exhibit a dose-dependent toxicity with illuminated TAPP. Our results suggest that even sub-minimum inhibitory concentrations of photo-activated TAPP could be used to boost the activity of waning antibiotics. This may play an important role in treatments reliant on antibiotic controlled release systems where augmentation with photo-active agents could extend their efficacy.
Insights
Combining photodynamic therapy with antibiotics shows promise for treating resistant Staphylococcal infections. Photoactivated meso-tetra (4-aminophenyl) porphine (TAPP) enhances antibiotic effectiveness against bacteria like MRSA.
Area of Science:
- Photomedicine
- Antimicrobial Resistance
- Bacteriology
Background:
- Antibiotic resistance in Staphylococcal infections poses a significant therapeutic challenge.
- Antimicrobial combination strategies, including photodynamic therapy (PDT), are being explored to overcome resistance.
- Meso-tetra (4-aminophenyl) porphine (TAPP) is a cationic porphyrin investigated for its antimicrobial potential.
Purpose of the Study:
- To investigate the combined efficacy of antibiotics and photoactivated TAPP against Staphylococcus aureus.
- To evaluate the potential of PDT-antibiotic combinations in combating antibiotic-resistant bacterial strains.
Main Methods:
- Characterization of the antimicrobial activity of photoactivated TAPP against Staphylococcus aureus.
- Assessment of TAPP's activity in the presence of radical scavengers and its reactivation potential.
- Evaluation of combination therapies using TAPP with various antibiotics (chloramphenicol, tobramycin, ceftriaxone, vancomycin) against S. aureus, MRSA, S. epidermidis, and E. coli.
- Assessment of TAPP's phototoxicity on eukaryotic cells.
Main Results:
- Photoactivated TAPP exhibits antimicrobial activity, which is reduced by radical scavengers but can be reactivated.
- TAPP's antimicrobial effect is additive with chloramphenicol and tobramycin against S. aureus and E. coli.
- Synergistic effects were observed with chloramphenicol and tobramycin against MRSA and S. epidermidis.
- Ceftriaxone and vancomycin showed limited augmentation of TAPP's activity against S. aureus.
- Illuminated TAPP demonstrated dose-dependent toxicity to eukaryotic cells.
Conclusions:
- Sub-minimum inhibitory concentrations of photoactivated TAPP can enhance the efficacy of certain antibiotics against resistant bacteria.
- PDT-antibiotic combinations offer a promising strategy to combat antibiotic resistance and extend the lifespan of existing antibiotics.
- This approach may be particularly relevant for antibiotic-controlled release systems.
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