title: Changes in glutathione-dependent redox status and mitochondrial energetic strategies are part of the adaptive response during the filamentation process in Candida albicans.
abstract: Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to systemic diseases called candidiasis. Its ability to grow in various morphological forms, such as unicellular budding yeast, filamentous pseudohyphae and hyphae, contributes to its survival in the diverse microenvironments it encounters in the host. During infection in vivo, C. albicans is faced with high levels of reactive oxygen species (ROS) generated by phagocytes, and the thiol-dependent redox status of the cells reflects their levels of oxidative stress. We investigated the role of glutathione during the transition between the yeast and hyphal forms of the pathogen, in relation to possible changes in mitochondrial bioenergetic pathways. Using various growth media and selective mutations affecting the filamentation process, we showed that C. albicans filamentation was always associated with a depletion of intracellular glutathione levels. Moreover, the induction of hypha formation resulted in general changes in thiol metabolism, including the oxidation of cell surface -SH groups and glutathione excretion. Metabolic adaptation involved tricarboxylic acid (TCA) cycle activation, acceleration of mitochondrial respiration and a redistribution of electron transfer pathways, with an increase in the contribution of the alternative oxidase and rotenone-insensitive dehydrogenase. Changes in redox status and apparent oxidative stress may be necessary to the shift to adaptive metabolic pathways, ensuring normal mitochondrial function and adenosine triphosphate (ATP) levels. The consumption of intracellular glutathione levels during the filamentation process may thus be the price paid by C. albicans for survival in the conditions encountered in the host.
authors.affiliation: Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, Université Paris-Diderot/CNRS (UMR 7592), 15 rue Hélène Brion, 75013 Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Guedouari
authors.affiliation: Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, Université Paris-Diderot/CNRS (UMR 7592), 15 rue Hélène Brion, 75013 Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Gergondey
authors.affiliation: Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, Université Paris-Diderot/CNRS (UMR 7592), 15 rue Hélène Brion, 75013 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Bourdais
authors.affiliation: Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, Université Paris-Diderot/CNRS (UMR 7592), 15 rue Hélène Brion, 75013 Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Vanparis
authors.affiliation: IPREM-LCABIE UMR 5254, 2 rue du président Angot, 64000 Pau, France.
authors.forename: A L
authors.initials: AL
authors.lastname: Bulteau
authors.affiliation: Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, Université Paris-Diderot/CNRS (UMR 7592), 15 rue Hélène Brion, 75013 Paris, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Camadro
authors.affiliation: Laboratoire Mitochondries, Métaux et Stress Oxydant, Institut Jacques Monod, Université Paris-Diderot/CNRS (UMR 7592), 15 rue Hélène Brion, 75013 Paris, France. Electronic address: auchere.francoise@ijm.univ-paris-diderot.fr.
authors.forename: F
authors.initials: F
authors.lastname: Auchère
mesh_terms: D000222:Adaptation, Physiological; D002176:Candida albicans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D002177:Candidiasis / Q000382:microbiology; D004579:Electron Transport; D004734:Energy Metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D025301:Hyphae / Q000254:growth & development / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D017382:Reactive Oxygen Species; D005978:Glutathione
keywords: Candida albicans; Filamentation; Glutathione; Metabolism; Mitochondria; Oxidative stress