Antimicrobial activity of water-soluble tetra-cationic porphyrins on Pseudomonas aeruginosa

This manuscript presents the cytotoxicity, antimicrobial activity, antibiofilm preliminary properties, and associated therapy with commercial drugs using water-soluble tetra-cationic porphyrins against Pseudomonas aeruginosa. Two commercial tetra-cationic porphyrins were tested against a standard strain of P. aeruginosa 01 (PA01) in antibacterial activity assays under dark conditions and irradiated with white light for 120 min. Porphyrin 4H2TMePor showed better antimicrobial activity and was chosen for further tests. Increased minimum inhibitory concentration was observed in the presence of reactive oxygen species, suggesting that photooxidation was mediated by the singlet oxygen production. In the time-kill curve assay, 4-H2TMePor inhibited bacterial growth in 90 min of irradiation. The checkerboard assay revealed synergistic interactions. Biofilms of the standard PA01 strain and three clinical isolates were formed. The biofilm destruction assay was more efficient for PA01, significantly reducing the biofilm biomass formed compared to the positive control. The associated treatment to destroy the biofilm potentiated a significant decrease in the biofilm biomass compared to the positive control. The photosensitizer did not damage human keratinocytes or mouse fibroblasts in the cytotoxicity assays, demonstrating the safety of using 4-H2TMePor. Atomic force microscopy indicated lower adhesion force, higher cell wall deformation, and higher dissipation energy in the treated control compared to untreated PA01. Given our findings, it is evident that water-soluble tetra-cationic porphyrins have excellent antimicrobial and a preliminary antibiofilm activity against Gram-negative bacteria, proving to be a potential photosensitizer for clinical use.

Automated summary

This manuscript investigates the cytotoxicity, antimicrobial activity, antibiofilm preliminary properties, and associated therapy of water-soluble tetra-cationic porphyrins against Pseudomonas aeruginosa. The study finds that porphyrin 4H2TMePor exhibits better antimicrobial activity and can inhibit bacterial growth through irradiation. The photosensitizer shows no toxicity to human keratinocytes or mouse fibroblasts. With its excellent antimicrobial and preliminary antibiofilm activity, water-soluble tetra-cationic porphyrins have the potential to be used as a clinical photosensitizer.