1887

Abstract

Hemiascomycetes, including the pathogen , 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 infections. To further characterize urea metabolism in we examined the function of seven putative urea transporters. Gene disruption established that Dur3, encoded by orf 19.781, is the predominant transporter. [C]Urea uptake was energy-dependent and decreased approximately sevenfold in a Δ mutant. and expression was strongly induced by urea, whereas the other putative transporter genes were induced less than twofold. Immediate induction of by urea was independent of its metabolism via Dur1,2, but further slow induction of required the Dur1,2 pathway. We investigated the role of the GATA transcription factors Gat1 and Gln3 in and expression. Urea induction of was reduced in a Δ mutant, strongly reduced in a Δ mutant, and abolished in a Δ Δ double mutant. In contrast, induction by urea was preserved in both single mutants but reduced in the double mutant, suggesting that additional signalling mechanisms regulate expression. These results establish Dur3 as the major urea transporter in and provide additional insights into the control of urea utilization by this pathogen.

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2011-01-01
2024-04-16
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References

  1. Caddick M. X., Peters D., Platt A. 1994; Nitrogen regulation in fungi. Antonie van Leeuwenhoek 65:169–177
    [Google Scholar]
  2. Cole G. T. 1997; Ammonia production by Coccidiodes immitis and its possible significance to the host–fungus interplay. In Host–Fungus Interplay pp 247–263 Edited by Stevens D. O. Bethesda, MD: National Foundation for Infectious Diseases;
    [Google Scholar]
  3. Collart M. A., Struhl K. 1994; NOT1(CDC39), NOT2(CDC36), NOT3, and NOT4 encode a global-negative regulator of transcription that differentially affects TATA-element utilization. Genes Dev 8:525–537
    [Google Scholar]
  4. Cooper T. G. 1982; Nitrogen metabolism in Saccharomyces cerevisiae. In The Molecular Biology of the Yeast Saccharomyces. pp 39–99 Edited by Strathern J. N., Jones E. W., Broach J. R. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  5. Cooper T. G., Lam C., Turoscy V. 1980; Structural analysis of the dur loci in S. cerevisiae : two domains of a single multifunctional gene. Genetics 94:555–580
    [Google Scholar]
  6. Cooper T. G., Ferguson D., Rai R., Bysani N. 1990; The GLN3 gene product is required for transcriptional activation of allantoin system gene expression in Saccharomyces cerevisiae . J Bacteriol 172:1014–1018
    [Google Scholar]
  7. Cove D. J. 1979; Genetic studies of nitrate assimilation in Aspergillus nidulans . Biol Rev Camb Philos Soc 54:291–327
    [Google Scholar]
  8. Cox G. M., Mukherjee J., Cole G. T., Casadevall A., Perfect J. R. 2000a; Urease as a virulence factor in experimental cryptococcosis. Infect Immun 68:443–448
    [Google Scholar]
  9. Cox K. H., Rai R., Distler M., Daugherty J. R., Coffman J. A., Cooper T. G. 2000b; Saccharomyces cerevisiae GATA sequences function as TATA elements during nitrogen catabolite repression and when Gln3p is excluded from the nucleus by overproduction of Ure2p. J Biol Chem 275:17611–17618
    [Google Scholar]
  10. Dabas N., Morschhäuser J. 2007; Control of ammonium permease expression and filamentous growth by the GATA transcription factors GLN3 and GAT1 in Candida albicans . Eukaryot Cell 6:875–888
    [Google Scholar]
  11. Dastidar S. G., Purandare N. M., Desai S. C. 1967; Growth requriements of Candida species. Indian J Exp Biol 5:228–232
    [Google Scholar]
  12. Davis M. A., Kelly J. M., Hynes M. J. 1993; Fungal catabolic gene regulation: molecular genetic analysis of the amdS gene of Aspergillus nidulans . Genetica 90:133–145
    [Google Scholar]
  13. Di Carlo F. J., Schultz A. S., Kent A. M. 1953; The mechanism of allantoin catabolism by yeast. Arch Biochem Biophys 44:468–474
    [Google Scholar]
  14. Dunkel N., Blass J., Rogers P. D., Morschhäuser J. 2008; Mutations in the multi-drug resistance regulator MRR1 , followed by loss of heterozygosity, are the main cause of MDR1 overexpression in fluconazole-resistant Candida albicans strains. Mol Microbiol 69:827–840
    [Google Scholar]
  15. Eaton K. A., Brooks C. L., Morgan D. R., Krakowka S. 1991; Essential role of urease in pathogenesis of gastritis induced by Helicobacter pylori in gnotobiotic piglets. Infect Immun 59:2470–2475
    [Google Scholar]
  16. Gillum A. M., Tsay E. Y., Kirsch D. R. 1984; Isolation of the Candida albicans gene for orotidine-5′-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol Gen Genet 198:179–182
    [Google Scholar]
  17. Ghosh S., Navarathna D. H., Roberts D. D., Cooper J. T., Atkin A. L., Petro T. M., Nickerson K. W. 2009; Arginine-induced germ tube formation in Candida albicans is essential for escape from murine macrophage line RAW 264.7. Infect Immun 77:1596–1605
    [Google Scholar]
  18. Jones B. D., Lockatell C. V., Johnson D. E., Warren J. W., Mobley H. L. 1990; Construction of a urease-negative mutant of Proteus mirabilis : analysis of virulence in a mouse model of ascending urinary tract infection. Infect Immun 58:1120–1123
    [Google Scholar]
  19. Köhrer K., Domdey H. 1991; Preparation of high molecular weight RNA. Methods Enzymol 194:398–405
    [Google Scholar]
  20. Krappmann S., Braus G. H. 2005; Nitrogen metabolism of Aspergillus and its role in pathogenicity. Med Mycol 43:Suppl. 1S31–S40
    [Google Scholar]
  21. Kulkarni R. K., Nickerson K. W. 1981; Nutritional control of dimorphism in Ceratocystis ulmi . Exp Mycol 5:148–154
    [Google Scholar]
  22. Limjindaporn T., Khalaf R. A., Fonzi W. A. 2003; Nitrogen metabolism and virulence of Candida albicans require the GATA-type transcriptional activator encoded by GAT1 . Mol Microbiol 50:993–1004
    [Google Scholar]
  23. Marzluf G. A. 1997; Genetic regulation of nitrogen metabolism in the fungi. Microbiol Mol Biol Rev 61:17–32
    [Google Scholar]
  24. Navarathna D. H., Roberts D. D. 2010; Candida albicans heme oxygenase and its product CO contribute to pathogenesis of candidemia and alter systemic chemokine and cytokine expression. Free Radic Biol Med 49:1561–1573
    [Google Scholar]
  25. Navarathna D. H., Hornby J. M., Hoerrmann N., Parkhurst A. M., Duhamel G. E., Nickerson K. W. 2005; Enhanced pathogenicity of Candida albicans pre-treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis. J Antimicrob Chemother 56:1156–1159
    [Google Scholar]
  26. Navarathna D. H., Nickerson K. W., Duhamel G. E., Jerrels T. R., Petro T. M. 2007; Exogenous farnesol interferes with the normal progression of cytokine expression during candidiasis in a mouse model. Infect Immun 75:4006–4011
    [Google Scholar]
  27. Navarathna D. H., Harris S. D., Roberts D. D., Nickerson K. W. 2010; Evolutionary aspects of urea utilization by fungi. FEMS Yeast Res 10:209–213
    [Google Scholar]
  28. Nozawa A., Takano J., Kobayashi M., von Wiren N., Fujiwara T. 2006; Roles of BOR1, DUR3, and FPS1 in boron transport and tolerance in Saccharomyces cerevisiae . FEMS Microbiol Lett 262:216–222
    [Google Scholar]
  29. Odds F. C. 1988 Candida and Candidiasis, 2nd edn. London: Bailliere Tindall;
    [Google Scholar]
  30. Pendrak M. L., Yan S. S., Roberts D. D. 2004a; Sensing the host environment: recognition of hemoglobin by the pathogenic yeast Candida albicans . Arch Biochem Biophys 426:148–156
    [Google Scholar]
  31. Pendrak M. L., Yan S. S., Roberts D. D. 2004b; Hemoglobin regulates expression of an activator of mating-type locus α genes in Candida albicans . Eukaryot Cell 3:764–775
    [Google Scholar]
  32. Pendrak M. L., Chao M. P., Yan S. S., Roberts D. D. 2004c; Heme oxygenase in Candida albicans is regulated by hemoglobin and is necessary for metabolism of exogenous heme and hemoglobin to α -biliverdin. J Biol Chem 279:3426–3433
    [Google Scholar]
  33. Pfaffl M. W. 2001; A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45
    [Google Scholar]
  34. Reuß O., Vik Å., Kolter R., Morschhäuser J. 2004; The SAT1 flipper, an optimized tool for gene disruption in Candida albicans . Gene 341:119–127
    [Google Scholar]
  35. Roon R. J., Levenberg B. 1972; Urea amidolyase. I. Properties of the enzyme from Candida utilis . J Biol Chem 247:4107–4113
    [Google Scholar]
  36. Roon R. J., Hampshire J., Levenberg B. 1972; Urea amidolyase. The involvement of biotin in urea cleavage. J Biol Chem 247:7539–7545
    [Google Scholar]
  37. Schwartz J. T., Allen L. A. 2006; Role of urease in megasome formation and Helicobacter pylori survival in macrophages. J Leukoc Biol 79:1214–1225
    [Google Scholar]
  38. Sentheshanmuganathan S., Nickerson W. J. 1962; Nutritional control of cellular form in Trigonopsis variabilis . J Gen Microbiol 27:437–449
    [Google Scholar]
  39. Yu J. J., Smithson S. L., Thomas P. W., Kirkland T. N., Cole G. T. 1997; Isolation and characterization of the urease gene ( URE ) from the pathogenic fungus Coccidioides immitis . Gene 198:387–391
    [Google Scholar]
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