title: Respiratory deficiency enhances the sensitivity of the pathogenic fungus Candida to photodynamic treatment.
abstract: Mucosal infections caused by the pathogenic fungus Candida are a significant infectious disease problem and are often difficult to eradicate because of the high frequency of resistance to conventional antifungal agents. Photodynamic treatment (PDT) offers an attractive therapeutic alternative. Previous studies demonstrated that filamentous forms and biofilms of Candida albicans were sensitive to PDT using Photofrin as a photosensitizer. However, early stationary phase yeast forms of C. albicans and Candida glabrata were not adversely affected by treatment. We report that the cationic porphyrin photosensitizer meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP-1363) is effective in PDT against yeast forms of C. albicans and C. glabrata. Respiratory-deficient (RD) strains of C. albicans and C. glabrata display a pleiotropic resistance pattern, including resistance to members of the azole family of antifungals, the salivary antimicrobial peptides histatins and other types of toxic stresses. In contrast to this pattern, RD mutants of both C. albicans and C. glabrata were significantly more sensitive to PDT compared to parental strains. These data suggest that intact mitochondrial function may provide a basal level of anti-oxidant defense against PDT-induced phototoxicity in Candida, and reveals pathways of resistance to oxidative stress that can potentially be targeted to increase the efficacy of PDT against this pathogenic fungus.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Yeissa
authors.initials: Y
authors.lastname: Chabrier-Roselló
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Foster
authors.forename: Soumya
authors.initials: S
authors.lastname: Mitra
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Haidaris
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D041221:Candida glabrata / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D025301:Hyphae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D018384:Oxidative Stress; D010101:Oxygen Consumption; 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; D017323:Dihematoporphyrin Ether