title: Cationic porphyrin-mediated photodynamic inactivation of Candida biofilms and the effect of miconazole.
abstract: The formation of biofilms by Candida and the increasing resistance of Candida species to antifungals contribute to the high recurrence rates of denture stomatitis. This increase has stimulated an interest in antimicrobial photodynamic therapy (aPDT) as an alternative treatment. We examined the photoactivity of the porphyrin-based photosensitizer, TMP-1363, against biofilms of C. albicans, C. glabrata, C. tropicalis and C. parapsilosis, and the effect of the combined use of miconazole and aPDT. Biofilms of three American Type Culture Collection (ATCC) strains and four clinical isolates developed on poly(methyl methacrylate) (PMMA) disks, were incubated with miconazole, followed by treatment with TMP-1363 for 30 min at 37°C. The plates were exposed to broadband visible light at a distance of 10 cm to the plate, for 30 min (irradiance at the surface of the plate: 32.5 mW/cm2). The metabolic activity of the biofilms was measured by the XTT assay. ATCC strains and C. glabrata 7531/06 were not sensitive to TMP-aPDT, whereas the metabolic activities of the remaining three clinical isolates were reduced to 64.2 ± 5.5% of controls. Miconazole at 25 μg/ml decreased the viability of all strains except the ATTCC strain C. albicans MYA274; however its combination with aPDT was effective against this strain, suggesting a synergistic interaction. Effects of miconazole and aPDT on C. albicans MYA 2732, C. albicans 6122/06 were additive. With C. tropicalis and C. parapsilosis, the combined treatment had a higher, but not entirely additive, cytotoxic effect. The combined use of miconazole and TMP-aPDT is advantageous in the treatment of biofilms of a number of Candida species and strains, but not all. The molecular basis of this differential response is not known.
authors.affiliation: Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA.|Department of Diagnostic Sciences, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Davies
authors.affiliation: Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gebremedhin
authors.affiliation: Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Yee
authors.affiliation: Department of Diagnostic Sciences, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Padilla
authors.affiliation: Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Duzgunes
authors.affiliation: Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Konopka
authors.affiliation: Department of Oral Pathology, University of Medical Sciences, Poznan, Poland. b.dorocka@gmail.com.
authors.forename: B
authors.initials: B
authors.lastname: Dorocka-Bobkowska
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000528:radiation effects; D002175:Candida / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D008027:Light; D008825:Miconazole / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; C057459:tetra(3-N-methylpyridyl)porphine; D008825:Miconazole