Photodynamic inactivation of multidrug-resistant Staphylococcus aureus by chlorin e6 and red light (λ=670 nm)

Multidrug-resistant Staphylococcus aureus (MDR-SA) are a frequent cause of antibiotic treatment refractory bacterial corneal infections. Photodynamic therapy (PDT) is being discussed as a putative treatment option to cure this type of bacterial infection. Here we tested the in vitro susceptibility of a set of 12 clinically derived MDR SA isolates with differing genetic backgrounds and antibiotic resistance profiles against photodynamic inactivation (PDI) by the porphyrin chlorin e6 (Ce6) and red light (lambda = 670 nm). All tested clinical isolates displayed a 5-log(10) reduction in viable cells by Ce6 and red light, when cells were preincubated with the photosensitizer at concentrations >= 128 mu M for 30 min in the dark, and a subsequent irradiation with light at lambda = 670 nm (power density: 31 mW/cm(2), absorbed dose: 18,6 J/cm(2)) was applied. Similarly, cells of the laboratory strain Newman required the same Ce6 pre-incubation and light dose for a 5-log(10) reduction in cell viability. Inactivation of crtM in strain Newman, which interferes with pigment production in S. aureus, rendered the mutant more susceptible to this PDT procedure, indicating that the level of resistance of S. aureus to this therapy form is affected by ability of the pathogen to produce the carotenoid pigment staphyloxanthin. Incubation of freshly explanted porcine corneas with a 0.5% Ce6 gel demonstrated that the photosensitizer can diffuse into and accumulate within the stroma of the cornea in concentrations found to be sufficient to yield a 5-log(10) reduction of the S. aureus cell pool in vitro. These data suggest that PDI with Ce6 and red light might be a promising new option for the treatment of MDR-SA induced corneal infections. (C) 2016 Elsevier B.V. All rights reserved.