title: Inhibition of specific electron transport pathways leads to oxidative stress and decreased Candida albicans proliferation.
abstract: Candida parapsilosis mitochondria contain three respiratory chains: the classical respiratory chain (CRC), a secondary parallel chain (PAR) and an "alternative" oxidative pathway (AOX). We report here the existence of similar pathways in C. albicans. To observe the capacity of each pathway to sustain yeast growth, C. albicans cells were cultured in the presence of inhibitors of these pathways. Antimycin A and KCN totally abrogated yeast growth, while rotenone did not prevent proliferation. Furthermore, rotenone promoted only partial respiratory inhibition. Lower concentrations of KCN that promote partial inhibition of respiration did not inhibit yeast growth, while partial inhibition of respiration with antimycin A did. Similarly, AOX inhibitor BHAM decreased O(2) consumption slightly but completely stunted cell growth. Reactive oxygen species production and oxidized glutathione levels were enhanced in cells treated with antimycin A or BHAM, but not rotenone or KCN. These findings suggest that oxidative stress prevents C. albicans growth.
authors.affiliation: Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ruy
authors.forename: Anibal E
authors.initials: AE
authors.lastname: Vercesi
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kowaltowski
mesh_terms: D000968:Antimycin A / Q000494:pharmacology; D002176:Candida albicans / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D004579:Electron Transport / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D024101:Mitochondrial Proteins; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption; D010940:Plant Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology; D000099188:Alternative Oxidase
chemical_list: D000968:Antimycin A; D005978:Glutathione; D006877:Hydroxamic Acids; D024101:Mitochondrial Proteins; D010088:Oxidoreductases; D010940:Plant Proteins; D017382:Reactive Oxygen Species; D012402:Rotenone; D014475:Uncoupling Agents; D000099188:Alternative Oxidase; C006696:benzohydroxamic acid