title: Dur3 is the major urea transporter in Candida albicans and is co-regulated with the urea amidolyase Dur1,2.
abstract: Hemiascomycetes, including the pathogen Candida albicans, acquire nitrogen from urea using the urea amidolyase Dur1,2, whereas all other higher fungi use primarily the nickel-containing urease. Urea metabolism via Dur1,2 is important for resistance to innate host immunity in C. albicans infections. To further characterize urea metabolism in C. albicans we examined the function of seven putative urea transporters. Gene disruption established that Dur3, encoded by orf 19.781, is the predominant transporter. [(14)C]Urea uptake was energy-dependent and decreased approximately sevenfold in a dur3Δ mutant. DUR1,2 and DUR3 expression was strongly induced by urea, whereas the other putative transporter genes were induced less than twofold. Immediate induction of DUR3 by urea was independent of its metabolism via Dur1,2, but further slow induction of DUR3 required the Dur1,2 pathway. We investigated the role of the GATA transcription factors Gat1 and Gln3 in DUR1,2 and DUR3 expression. Urea induction of DUR1,2 was reduced in a gat1Δ mutant, strongly reduced in a gln3Δ mutant, and abolished in a gat1Δ gln3Δ double mutant. In contrast, DUR3 induction by urea was preserved in both single mutants but reduced in the double mutant, suggesting that additional signalling mechanisms regulate DUR3 expression. These results establish Dur3 as the major urea transporter in C. albicans and provide additional insights into the control of urea utilization by this pathogen.
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1500, USA.
authors.forename: Dhammika H M L P
authors.initials: DHMLP
authors.lastname: Navarathna
authors.affiliation: Institut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany.
authors.forename: Aditi
authors.initials: A
authors.lastname: Das
authors.affiliation: Institut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Morschhäuser
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Nickerson
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1500, USA.
authors.forename: David D
authors.initials: DD
authors.lastname: Roberts
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology / Q000401:mortality; D002250:Carbon Radioisotopes / Q000378:metabolism; D019731:Carbon-Nitrogen Ligases / Q000378:metabolism*; D016469:Fungemia / Q000382:microbiology / Q000401:mortality; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D026901:Membrane Transport Proteins / Q000096:biosynthesis*; D051379:Mice; D016254:Mutagenesis, Insertional; D013194:Staining and Labeling / Q000379:methods; D016019:Survival Analysis; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014508:Urea / Q000378:metabolism*; D014774:Virulence; D000096982:Urea Transporters
chemical_list: D002250:Carbon Radioisotopes; D019731:Carbon-Nitrogen Ligases; D026901:Membrane Transport Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014508:Urea; D000096982:Urea Transporters; C480852:GAT1 protein, Candida albicans; C023270:urea carboxylase (hydrolyzing)