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: Candia 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 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 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 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: University Paris-Diderot / CNRS (Jacques Monod Institute), Mitochondria, Metals and Oxidative Stress Laboratory, France.
authors.forename: Guedouari
authors.initials: G
authors.lastname: Hala
authors.affiliation: University Paris-Diderot / CNRS (Jacques Monod Institute), Mitochondria, Metals and Oxidative Stress Laboratory, France.
authors.forename: Gergondey
authors.initials: G
authors.lastname: Rachel
authors.affiliation: University Paris-Diderot / CNRS (Jacques Monod Institute), Mitochondria, Metals and Oxidative Stress Laboratory, France.
authors.forename: Bourdais
authors.initials: B
authors.lastname: Arthur
authors.affiliation: University Paris-Diderot / CNRS (Jacques Monod Institute), Mitochondria, Metals and Oxidative Stress Laboratory, France.
authors.forename: Vanparis
authors.initials: V
authors.lastname: Océane
authors.affiliation: UMR 5254 (IPREM), LCABIE, France.
authors.forename: Bulteau
authors.initials: B
authors.lastname: Anne-Laure
authors.affiliation: University Paris-Diderot / CNRS (Jacques Monod Institute), Mitochondria, Metals and Oxidative Stress Laboratory, France.
authors.forename: Camadro
authors.initials: C
authors.lastname: Jean-Michel
authors.affiliation: University Paris-Diderot / CNRS (Jacques Monod Institute), Mitochondria, Metals and Oxidative Stress Laboratory, France. Electronic address: auchere.francoise@ijm.univ-paris-diderot.fr.
authors.forename: Auchère
authors.initials: A
authors.lastname: Françoise