title: A family of glutathione peroxidases contributes to oxidative stress resistance in Candida albicans.
abstract: Candida albicans is a well-adapted human commensal but is also a facultative pathogen that can cause superficial and systemic infections. Its remarkable capacity to thrive within the human host relies on its ability to adapt and respond to the local environment of different niches. C. albicans is able to cope with oxidative stress in a coordinated fashion via upregulation of different protective mechanisms. Here, we unravel the role of a family of glutathione peroxidase (GPx), designated Gpx31, Gpx32, and Gpx33, in oxidative stress resistance. We show that GPx activity in C. albicans is induced upon exposure to peroxides and that this enzymatic activity is required for full resistance to oxidative stress. The GPx activity relies on the presence of GPX31, with no apparent contribution from GPX32 and GPX33 during in vitro short-term (3 h) exposure to peroxides. However, a triple gpx31-33Δ/Δ mutant exhibited a more pronounced sensitivity than a single gpx31Δ/Δ mutant on solid media in the presence of oxidants, suggesting that GPX32 and GPX33 may be involved in long-term adaptation to oxidative stress. Interestingly, reintegration of a single allele of GPX31 was sufficient to restore the wild-type phenotype in both the single and triple mutants. We found that mutants lacking GPX31-33 were more susceptible to killing by phagocytic cells, suggesting that GPxs are required for full resistance to innate immune effector cells. Despite the sensitivity to oxidative stress and phagocytes, these mutants were not affected in their virulence in the chicken embryo model of candidiasis.
authors.affiliation: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology.
authors.forename: Pedro
authors.initials: P
authors.lastname: Miramón
authors.forename: Christine
authors.initials: C
authors.lastname: Dunker
authors.forename: Lydia
authors.initials: L
authors.lastname: Kasper
authors.forename: Ilse D
authors.initials: ID
authors.lastname: Jacobsen
authors.forename: Dagmar
authors.initials: D
authors.lastname: Barz
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D004361:Drug Tolerance; D017353:Gene Deletion; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D050296:Microbial Viability / Q000187:drug effects; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress; D010545:Peroxides / Q000633:toxicity*; D014774:Virulence
chemical_list: D016877:Oxidants; D010545:Peroxides; D005979:Glutathione Peroxidase
keywords: Candida albicans; glutathione peroxidase; oxidative stress; phagocytes