title: Photodynamic inactivation of multidrug-resistant Staphylococcus aureus by chlorin e6 and red light (λ=670nm).
abstract: 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 (λ=670nm). All tested clinical isolates displayed a 5-log10 reduction in viable cells by Ce6 and red light, when cells were preincubated with the photosensitizer at concentrations ≥128μM for 30min in the dark, and a subsequent irradiation with light at λ=670nm (power density: 31mW/cm(2), absorbed dose: 18,6J/cm(2)) was applied. Similarly, cells of the laboratory strain Newman required the same Ce6 pre-incubation and light dose for a 5-log10 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-log10 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.
authors.affiliation: Institute of Medical Microbiology and Hygiene, Saarland University, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Winkler
authors.affiliation: Department of Physics, University of Kaiserslautern, Germany.
authors.forename: Carole
authors.initials: C
authors.lastname: Simon
authors.affiliation: Institute of Medical Microbiology and Hygiene, Saarland University, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Finke
authors.affiliation: Institute of Medical Microbiology and Hygiene, Saarland University, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Bleses
authors.affiliation: Institute of Medical Microbiology and Hygiene, Saarland University, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Birke
authors.affiliation: Department of Ophthalmology, Saarland University Medical Center, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Szentmáry
authors.affiliation: ApoCare Pharma GmbH, Bielefeld, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Hüttenberger
authors.affiliation: Institute of Experimental Ophthalmology, Saarland University, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Eppig
authors.affiliation: Department of Ophthalmology, Saarland University Medical Center, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Stachon
authors.affiliation: Institute of Experimental Ophthalmology, Saarland University, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Langenbucher
authors.affiliation: Department of Physics, University of Kaiserslautern, Germany.
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Foth
authors.affiliation: Institute of Medical Microbiology and Hygiene, Saarland University, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Department of Ophthalmology, Saarland University Medical Center, Germany.
authors.forename: Berthold
authors.initials: B
authors.lastname: Seitz
authors.affiliation: Institute of Medical Microbiology and Hygiene, Saarland University, Germany. Electronic address: markus.bischoff@uks.eu.
authors.forename: Markus
authors.initials: M
authors.lastname: Bischoff
mesh_terms: D000818:Animals; D002735:Chlorophyllides; D003319:Corneal Stroma / Q000378:metabolism; D004058:Diffusion; D007700:Kinetics; D008027:Light; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects*; D050296:Microbial Viability / Q000187:drug effects* / Q000528:radiation effects*; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D010858:Pigmentation / Q000187:drug effects / Q000528:radiation effects; D011166:Porphyrins / Q000378:metabolism / Q000494:pharmacology*; D013552:Swine
chemical_list: D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin
keywords: Chlorin e6; Diffusion; Multidrug-resistant Staphylococcus aureus; Photodynamic therapy; Pigmentation