PMID- 22332981 OWN - NLM STAT- MEDLINE DCOM- 20130117 LR - 20120710 IS - 1751-1097 (Electronic) IS - 0031-8655 (Linking) VI - 88 IP - 4 DP - 2012 Jul-Aug TI - Cell survival and altered gene expression following photodynamic inactivation of Paracoccidioides brasiliensis. PG - 992-1000 LID - 10.1111/j.1751-1097.2012.01112.x [doi] AB - Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidioides brasiliensis. Currently, the treatment approach involves the use of antifungal drugs and requires years of medical therapy, which can induce nephrotoxicity and lead to resistance in yeast strains. Photodynamic inactivation (PDI) is a new therapy capable of killing microorganisms via the combination of a nontoxic dye with visible light to generate toxic reactive oxygen species (ROS). We investigated the phototoxic effect of 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin (TMPyP), a cationic porphyrin, on the survival of P. brasiliensis following exposure to light. Phototoxicity was found to depend on both the fluence and concentration of the photosensitizer (PS). Although the biological effects of PDI are known, the molecular mechanisms underlying the resultant damage to cells are poorly defined. Therefore, we evaluated the molecular response to PDI-induced oxidative stress by gene transcription analysis. We selected genes associated with the high-osmolarity glycerol (HOG)-mitogen-activated protein kinase (MAPK) pathway and antioxidant enzymes. The genes analyzed were all overexpressed after PDI treatment, suggesting that the oxidative stress generated in our experimental conditions induces antioxidant activity. In addition to PDI-induced gene expression, there was high cell mortality, suggesting that the antioxidant response was not sufficient to avoid fungal mortality. CI - (c) 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology (c) 2012 The American Society of Photobiology. FAU - Almeida, Luciane M AU - Almeida LM AD - Universidade Estadual de Goias (UEG), UnU-Ipameri, GO, Brazil. almeidalm@hotmail.com FAU - Zanoelo, Fabiana F AU - Zanoelo FF FAU - Castro, Kelly P AU - Castro KP FAU - Borissevitch, Iouri E AU - Borissevitch IE FAU - Soares, Celia M A AU - Soares CM FAU - Goncalves, Pablo J AU - Goncalves PJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120308 PL - United States TA - Photochem Photobiol JT - Photochemistry and photobiology JID - 0376425 RN - 0 (Fungal Proteins) RN - 0 (Photosensitizing Agents) RN - 0 (Porphyrins) RN - 0 (Reactive Oxygen Species) RN - 38673-65-3 (tetra(4-N-methylpyridyl)porphine) RN - EC 1.- (Oxidoreductases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Colony Count, Microbial MH - Dose-Response Relationship, Drug MH - Fungal Proteins/genetics/metabolism MH - Gene Expression Regulation MH - Light MH - Microbial Viability/drug effects/radiation effects MH - Mitogen-Activated Protein Kinases/genetics/metabolism MH - Oxidative Stress/drug effects/radiation effects MH - Oxidoreductases/genetics/metabolism MH - Paracoccidioides/*drug effects/metabolism/*radiation effects MH - Photosensitizing Agents/chemistry/*pharmacology MH - Porphyrins/chemistry/*pharmacology MH - Reactive Oxygen Species/agonists/metabolism MH - Transcription, Genetic EDAT- 2012/02/16 06:00 MHDA- 2013/01/18 06:00 CRDT- 2012/02/16 06:00 PHST- 2012/02/16 06:00 [entrez] PHST- 2012/02/16 06:00 [pubmed] PHST- 2013/01/18 06:00 [medline] AID - 10.1111/j.1751-1097.2012.01112.x [doi] PST - ppublish SO - Photochem Photobiol. 2012 Jul-Aug;88(4):992-1000. doi: 10.1111/j.1751-1097.2012.01112.x. Epub 2012 Mar 8.