Superoxide dismutases in Candida albicans: transcriptional regulation and functional characterization of the hyphal-induced SOD5 gene.
Superoxide dismutases (SOD) convert superoxide radicals into less damaging hydrogen peroxide. The opportunistic human pathogen Candida albicans is known to express CuZnSOD (SOD1) and MnSOD (SOD3) in the cytosol and MnSOD (SOD2) in the mitochondria. We identified three additional CuZn-containing superoxide dismutases, SOD4, SOD5, and SOD6, within the sequence of the C. albicans genome. The transcription of SOD5 was up-regulated during the yeast to hyphal transition of C. albicans, and SOD5 was induced when C. albicans cells were challenged with osmotic or with oxidative stresses. SOD5 transcription was also increased when cells were grown on nonfermentable substrates as the only carbon source. The Rim101p transcription factor was required for all inductions observed, whereas the Efg1p transcription factor was specifically needed for serum-modulated expression. Deletion of SOD5 produced a viable mutant strain that showed sensitivity to hydrogen peroxide when cells were grown in nutrient-limited conditions. Sod5p was found to be necessary for the virulence of C. albicans in a mouse model of infection. However, the sod5 mutant strain showed the same resistance to macrophage attack as its parental strain, suggesting that the loss of virulence in not due to an increased sensitivity to macrophage attack.
Martchenko
Mikhail
M
Department of Biology, McGill University, Montreal, Quebec, Canada H3A 1B1.
Alarco
Anne-Marie
AM
Harcus
Doreen
D
Whiteway
Malcolm
M
D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans / Q000201:enzymology* / Q000472:pathogenicity; D002177:Candidiasis / Q000201:enzymology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation; D018384:Oxidative Stress / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; C489602:RIM101 protein, Candida albicans; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase