title: Development of oxidative stress tolerance resulted in reduced ability to undergo morphologic transitions and decreased pathogenicity in a t-butylhydroperoxide-tolerant mutant of Candida albicans.
abstract: We tested the hypothesis that adaptation of Candida albicans to chronic oxidative stress inhibits the formation of hyphae and reduces pathogenicity. Candida albicans cells were exposed to increasing concentrations of t-butylhydroperoxide (tBOOH), a lipid peroxidation-accelerating agent, and mutants with heritable tBOOH tolerance were isolated. Hypha formation by the mutants was negligible on Spider agar, indicating that the development of oxidative stress tolerance prevented Candida cells from undergoing dimorphic switches. One of the mutants, C. albicans AF06, was five times less pathogenic in mice than its parental strain, due to its reduced germ tube-, pseudohypha- and hypha-forming capability, and decreased phospholipase secretion. An increased oxidative stress tolerance may therefore be disadvantageous when this pathogen leaves blood vessels and invades deep organs. The AF06 mutant was characterized by high intracellular concentrations of endogenous oxidants, reduced monounsaturated and polyunsaturated fatty acid contents, the continuous induction of the antioxidative defense system, decreased cytochrome c-dependent respiration, and increased alternative respiration. The mutation did not influence growth rate, cell size, cell surface, cellular ultrastructures, including mitochondria, or recognition by human polymorphonuclear leukocytes. The selection of oxidative stress-tolerant respiratory Candida mutants may also occur in vivo, when reduced respiration helps the fungus to cope with antimycotic agents.
authors.affiliation: Department of Microbial Biotechnology and Cell Biology, Faculty of Science, University of Debrecen, Debrecen, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fekete
authors.forename: Tamás
authors.initials: T
authors.lastname: Emri
authors.forename: Agnes
authors.initials: A
authors.lastname: Gyetvai
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Gazdag
authors.forename: Miklós
authors.initials: M
authors.lastname: Pesti
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Varga
authors.forename: József
authors.initials: J
authors.lastname: Balla
authors.forename: Csaba
authors.initials: C
authors.lastname: Cserháti
authors.forename: Levente
authors.initials: L
authors.lastname: Emody
authors.forename: Lajos
authors.initials: L
authors.lastname: Gergely
authors.forename: István
authors.initials: I
authors.lastname: Pócsi
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology*; D048429:Cell Size; D004271:DNA, Fungal / Q000737:chemistry; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D025301:Hyphae / Q000254:growth & development; D015227:Lipid Peroxidation / Q000502:physiology; D051379:Mice; D009154:Mutation / Q000235:genetics*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D037521:Virulence Factors / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D004271:DNA, Fungal; D037521:Virulence Factors; D020122:tert-Butylhydroperoxide