Alternative oxidase induction protects Candida albicans from respiratory stress and promotes hyphal growth

Abstract

AbstractThe human fungal pathogenCandida albicanspossesses two genes expressing a cyanide-insensitive Alternative Oxidase (Aox) enzymes in addition to classical and parallel electron transfer chains (ETC). In this study, we examine the role of Aox inC.albicansunder conditions of respiratory stress, which may be inflicted during its interaction with the human host or co-colonising bacteria. We find that the level of Aox expression is sufficient to modulate resistance to classical ETC inhibition under respiratory stress and are linked to gene expression changes that can promote both survival and pathogenicity. For example we demonstrate that Aox function is important for the regulation of filamentation inC.albicansand observe that cells lacking Aox function lose virulence in a zebrafish infection model. Our investigations also identify that pyocyanin, a phenazine produced by the co-colonising bacteriumPseudomonas aeruginosa, inhibits Aox-based respiration inC.albicans. These results suggest that Aox plays important roles within respiratory stress response pathways whichC.albicansmay utilise both as a commensal organism and as a pathogen.