First evidence of photoinactivation of rapidly growing mycobacteria by tetra-cationic porphyrins with peripheral cisplatin.

This manuscript describes the evaluation of the photoinactivation of cationic meso-tetra(pyridyl)porphyrins combined with cisplatin as photosensitizers (PS) for the photodynamic inactivation of Rapidly Growing Mycobacteria (RGM) strains. Two porphyrin derivatives, 3-cis-PtTPyP and 4-cis-PtTPyP, were synthesized according to methodologies previously described in the literature. The Antimicrobial Photodynamic Therapy (aPDT) experiments were conducted on different RGM strains, including Mycobacteroides abscessus subsp. abscessus (ATCC 19977), Mycolicibacterium fortuitum (ATCC 6841), Mycobacteroides abscessus subsp. massiliense (ATCC 48898), and Mycolicibacterium smegmatis (ATCC 700084), using appropriate concentrations of PS under conditions of exposure to a white-light source for 90 min (irradiance of 50 mW cm‒2 and a total light dosage of 270 J cm‒2). The results showed that the meta-isomeric porphyrin (3-cis-PtTPyP) was more photo-effective, significantly reducing the concentration of viable mycobacteria and inducing morphological, mechanical, and electrostatic changes in the bacterial structure. Combining photoinactivation with antimicrobials resulted in synergistic and additive effects, suggesting that this porphyrin can act as a therapeutic adjuvant or even a substitute for the conventional treatment of mycobacterial diseases. The observed photoinactivation profile, with rapid and effective bactericidal action, reinforces this PS class's potential for applications in several fields.