title: Glutathione reductase/glutathione is responsible for cytotoxic elemental sulfur tolerance via polysulfide shuttle in fungi.
abstract: Fungi that can reduce elemental sulfur to sulfide are widely distributed, but the mechanism and physiological significance of the reaction have been poorly characterized. Here, we purified elemental sulfur-reductase (SR) and cloned its gene from the elemental sulfur-reducing fungus Fusarium oxysporum. We found that NADPH-glutathione reductase (GR) reduces elemental sulfur via glutathione as an intermediate. A loss-of-function mutant of the SR/GR gene generated less sulfide from elemental sulfur than the wild-type strain. Its growth was hypersensitive to elemental sulfur, and it accumulated higher levels of oxidized glutathione, indicating that the GR/glutathione system confers tolerance to cytotoxic elemental sulfur by reducing it to less harmful sulfide. The SR/GR reduced polysulfide as efficiently as elemental sulfur, which implies that soluble polysulfide shuttles reducing equivalents to exocellular insoluble elemental sulfur and generates sulfide. The ubiquitous distribution of the GR/glutathione system together with our findings that GR-deficient mutants derived from Saccharomyces cerevisiae and Aspergillus nidulans reduced less sulfur and that their growth was hypersensitive to elemental sulfur indicated a wide distribution of the system among fungi. These results indicate a novel biological function of the GR/glutathione system in elemental sulfur reduction, which is distinguishable from bacterial and archaeal mechanisms of glutathione- independent sulfur reduction.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sato
authors.forename: Kanami
authors.initials: K
authors.lastname: Shimatani
authors.forename: Kensaku
authors.initials: K
authors.lastname: Fujita
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Abe
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Shimizu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujii
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Naoki
authors.initials: N
authors.lastname: Takaya
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000187:drug effects / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005670:Fusarium / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010084:Oxidation-Reduction / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013440:Sulfides / Q000378:metabolism*; D013455:Sulfur / Q000494:pharmacology*
chemical_list: D005656:Fungal Proteins; D013440:Sulfides; D013455:Sulfur; C032915:polysulfide; D005980:Glutathione Reductase; D005978:Glutathione