Determination of the antibacterial efficacy of a new porphyrin-based photosensitizer against MRSA ex vivo.
Following extensive in vitro screening of new photosensitizers the purpose of the present study was to examine penetration as well as antibacterial efficacy of a lead photosensitizer against MRSA using an ex vivo porcine skin model. Two different applications were performed: (i) preincubation of bacteria in solution with a porphyrin-based photosensitizer XF73 and subsequent application on the ex vivo porcine skin; (ii) application of pure bacteria on the explants followed by an incubation with XF73 in a water-ethanol formulation for up to 60 min under occlusion. The localisation of XF73 was restricted to the stratum corneum. Different concentrations (0-10 microM) of XF73 and different incubation times (5-60 min) were used to determine phototoxicity against methicillin-resistant and methicillin-sensitive S. aureus, which was applied on the explants. Preincubation of S. aureus with 0.1 microM XF73 in solution prior to the application of these XF73-incubated bacteria on the skin demonstrates a higher efficacy (>3 log10) after irradiation. Antibacterial photodynamic inactivation resulted in a approximately 1 log10 (0.1 microM)-3.64+/-0.035 (10 microM) log10 growth reduction independently of the antibiotic resistance pattern of used S. aureus strains. Irradiation of applied bacteria without photosensitizer incubation did not show any marked decrease (<1 log10) of bacteria cell number, indicating a significant phototoxicity of the XF73. Histological evaluations of untreated and treated skin areas upon irradiation within 24 h showed no significant degree of necrosis or apoptosis determined by TUNEL-assay indicating that the porcine skin is still vital. This study demonstrates that this XF73 porphyrin-based photosensitizer had concentration-dependent differences in killing efficacy of MRSA in comparison to skin cells using an ex vivo porcine skin model. The results described here imply that topical delivery of XF73 may be considered as a possible treatment in patients with superficial infections of the skin.
Maisch
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Department of Dermatology, University of Regensburg, Klinik und Poliklinik für Dermatologie, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany. tim.maisch@klinik.uni-regensburg.de
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016106:Methicillin Resistance; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D012867:Skin / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000528:radiation effects*; D013552:Swine
D000900:Anti-Bacterial Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; C521987:XF73 compound