title: Adaptation ofCandida albicansto Reactive Sulfur Species.
abstract: Candida albicansis an opportunistic fungal pathogen that is highly resistant to different oxidative stresses. How reactive sulfur species (RSS) such as sulfite regulate gene expression and the role of the transcription factor Zcf2 and the sulfite exporter Ssu1 in such responses are not known. Here, we show thatC. albicansspecifically adapts to sulfite stress and that Zcf2 is required for that response as well as induction of genes predicted to remove sulfite from cells and to increase the intracellular amount of a subset of nitrogen metabolites. Analysis of mutants in the sulfate assimilation pathway show that sulfite conversion to sulfide accounts for part of sulfite toxicity and that Zcf2-dependent expression of theSSU1sulfite exporter is induced by both sulfite and sulfide. Mutations in theSSU1promoter that selectively inhibit induction by the reactive nitrogen species (RNS) nitrite, a previously reported activator ofSSU1, support a model forC. albicansin which Cta4-dependent RNS induction and Zcf2-dependent RSS induction are mediated by parallel pathways, different fromS. cerevisiaein which the transcription factor Fzf1 mediates responses to both RNS and RSS. Lastly, we found that endogenous sulfite production leads to an increase in resistance to exogenously added sulfite. These results demonstrate thatC. albicanshas a unique response to sulfite that differs from the general oxidative stress response, and that adaptation to internal and external sulfite is largely mediated by one transcription factor and one effector gene.
authors.affiliation: Department of Biosciences, Rice University, Houston, Texas 77005.
authors.forename: Yasmin
authors.identifier: 0000-0002-1432-6592
authors.initials: Y
authors.lastname: Chebaro
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas Medical School, Houston, Texas 77030.
authors.forename: Michael
authors.initials: M
authors.lastname: Lorenz
authors.affiliation: Department of Biosciences, Rice University, Houston, Texas 77005.
authors.forename: Alice
authors.initials: A
authors.lastname: Fa
authors.affiliation: Department of Biosciences, Rice University, Houston, Texas 77005.
authors.forename: Rui
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of Biosciences, Rice University, Houston, Texas 77005 gustin@rice.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Gustin
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D027321:Anion Transport Proteins / Q000235:genetics*; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D015966:Gene Expression Regulation, Fungal; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D011401:Promoter Regions, Genetic; D026361:Reactive Nitrogen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D013447:Sulfites / Q000378:metabolism / Q000494:pharmacology; D013455:Sulfur / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D027321:Anion Transport Proteins; C090870:FZF1 protein, S cerevisiae; D026361:Reactive Nitrogen Species; D029701:Saccharomyces cerevisiae Proteins; C108311:Ssu1 protein, S cerevisiae; D013447:Sulfites; D014157:Transcription Factors; D013455:Sulfur
keywords: Candida albicans; ZCF2; sulfide; sulfite