Author | Gomes Junior, Rafael Araújo | |
Author | Silva, Roberto Santana da | |
Author | Lima, Renata Galvão de | |
Author | Santos, Marcos André Vannier dos | |
Access date | 2017-11-17T16:34:32Z | |
Available date | 2017-11-17T16:34:32Z | |
Document date | 2017 | |
Citation | GOMES JUNIOR, R. A. et al. Antifungal mechanism of [RuIII(NH3)4catechol]+ complex on fluconazole-resistant Candida tropicalis. FEMS Microbiology Letters, v. 364, n. 9, 2017 | pt_BR |
ISSN | 0378-1097 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/23262 | |
Language | eng | pt_BR |
Publisher | Oxford University Press | pt_BR |
Rights | open access | |
Subject in Portuguese | Candida tropicalis | pt_BR |
Subject in Portuguese | Resistente ao fluconazol | pt_BR |
Subject in Portuguese | Complexo de rutênio | pt_BR |
Subject in Portuguese | catecol, agentes antifúngicos, candidíase | pt_BR |
Title | Antifungal mechanism of [RuIII(NH3)4catechol]+ complex on fluconazole-resistant Candida tropicalis | pt_BR |
Type | Article | |
DOI | 10.1093/femsle/fnx073 | |
Abstract | Candidiasis, a major opportunistic mycosis caused by Candida sp., may comprise life-threatening systemic infections. The incidence of non-albicans species is rising, particularly in South America and they are frequently drug resistant, causing unresponsive cases. Thus, novel antimycotic agents are required. Here we tested the antifungal activity of [RuIII(NH3)4catechol]+ complex (RuCat), approaching possible action mechanisms on fluconazole-resistant Candida tropicalis. RuCat significantly (P < 0.05) inhibited the growth and viability of C. tropicalis dose-dependently (IC50 20.3 μM). Cytotoxicity of RuCat upon murine splenocytes was lower (Selectivity Index = 16). Scanning electron microscopy analysis showed pseudohyphae formation, yeast aggregation and surface damage. RuCat-treated samples investigated by transmission electron microscopy showed melanin granule trafficking to cell surfaces and extracellular milieu. Surface-adherent membrane fragments and extracellular debris were also observed. RuCat treatment produced intense H2DCFDA labeling, indicating reactive oxygen species (ROS) production which caused increased lipoperoxidation. ROS are involved in the fungicidal effect as N-acetyl-L-cysteine completely restored cell viability. Calcofluor White chitin staining suggests that 70 or 140 μM RuCat treatment for 2 h affected cell-wall structure. PI labeling indicated necrotic cell death. The present data indicate that RuCat triggers ROS production, lipoperoxidation and cell surface damage, culminating in selective necrotic death of drug-resistant C. tropicalis. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil | pt_BR |
Affilliation | Universidade Federal de Uberlândia. Faculdade de Ciências Integradas do Pontal. Uberlânida, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Subject | Candida tropicalis | pt_BR |
Subject | fluconazole-resistant | pt_BR |
Subject | Ruthenium complex | pt_BR |
Subject | catechol, antifungal agents, candidiasis | pt_BR |