Porphyrin Modifications for Enhanced Photodynamic Inactivation of Microbial Pathogens

Diseases caused by bacteria affecting the upper respiratory tract are a concern in the healthcare system, according to the World Health Organization. Multidrug-resistant Klebsiella pneumoniae is considered a critical pathogen due to its antibiotic resistance. Photodynamic therapy (PDT) is a promising alternative, using photosensitizers (PSs) and light to generate reactive oxygen species for bacterial inactivation. This study evaluated porphyrin derivatives with different substituents against K. pneumoniae. The bacteria were incubated for 1h with different meso-substituted porphyrins (cationic, neutral, and negatively charged) in a range of concentrations. Samples were irradiated in the therapeutic window at different light doses. Treatments were evaluated by viability assay. Cationic imidazolyl-derived porphyrins achieved >3 log bacterial reductions under irradiation, and effectiveness depended on PS concentration and light dose. Designed porphyrins show promise for K. pneumoniae PDT, supporting PDT as a non-antibiotic strategy against resistant infections. Understanding substituent effects aids the design of next-generation antimicrobial photosensitizers.