Susceptibility of methicillin-resistant Staphylococcus aureus to photodynamic antimicrobial chemotherapy with α-D-galactopyranosyl zinc phthalocyanines: in vitro study

The incidence of methicillin-resistant strains of Staphylococcus aureus (MRSA) is increasing globally, making urgent the discovery of novel alternative therapies for infections. Photodynamic antimicrobial chemotherapy (PACT), based on oxidative damage to subcellular structures, has the advantage of circumventing multidrug resistance, and is becoming a potential therapeutic modality for methicillin-resistant bacteria. The key to PACT is photosensitization. This study demonstrates the efficiency of PACT using alpha-d-galactopyranosyl zinc phthalocyanines (T1-T4) for the photosensitization of MRSA, Escherichia coli, and Pseudomonas aeruginosa. Bacterial suspensions were illuminated with 650-nm light from a semiconductor laser at 0.2 W/cm(2), and the energy density was maintained at 6 J/cm(2) in the presence of different concentrations of photosensitizer. The treatment response was evaluated based on the numbers of bacterial colony-forming units. PACT with these phthalocyanines strongly affected MRSA, but weakly affected E. coli and P. aeruginosa. The efficiency of PACT on MRSA with these four phthalocyanine compounds decreased in the order T1 > T2 > T3 > T4. T1-PACT eliminated > 99 % of MRSA in a concentration range of 25-50 mu M and at an energy density of 6 J/cm(2). Uptake measurements revealed that the PACT effect correlated with the bacterial uptake of the photosensitizer and that 4-30-fold more T1 than T2-T4 was taken up by the MRSA strain, which was confirmed with laser confocal microscopy. These data suggest that T1 is an efficient PACT photosensitizer for MRSA.