1887

Abstract

, unlike , was able to use extracellular haemin as an iron source. Haemin uptake kinetics by cells showed two phases: a rapid phase of haemin binding (with a of about 0·2 μM) followed by a slower uptake phase. Both phases were strongly induced in iron-deficient cells compared to iron-rich cells. Haemin uptake did not depend on the previously characterized reductive iron uptake system and siderophore uptake system. , encoding a putative haem oxygenase, was shown to be required for iron assimilation from haemin. A double Δ mutant was constructed. This mutant could not grow with haemin as the sole iron source, although haemin uptake was not affected. The three different iron uptake systems (reductive, siderophore and haemin) were regulated independently and in a complex manner. expression was induced by iron deprivation, by haemin and by a shift of temperature from 30 to 37 °C. expression was strongly deregulated in a Δ mutant but not in a Δ mutant. colonies forming on agar plates with haemin as the sole iron source showed a very unusual morphology. Colonies were made up of tubular structures that were organized into a complex network. The effect of haemin on filamentation was increased in the double Δ mutant. This study provides the first experimental evidence that haem oxygenase is required for iron assimilation from haem by a pathogenic fungus.

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2003-03-01
2020-06-03
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References

  1. Ardon O, Bussey H, Philpott C, Ward D, Davis-Kaplan S, Verroneau S, Jiang B., Kaplan J. 2001; Identification of a Candida albicans ferrichrome transporter and its characterization by expression in Saccharomyces cerevisiae . J Biol Chem276:43049–43055
    [Google Scholar]
  2. Braun B. R., Johnson A. D. 1997; Control of filament formation in Candida albicans by the transcriptional repressor TUP1 . Science277:105–109
    [Google Scholar]
  3. Brown A. J., Gow N. A. 1999; Regulatory networks controlling Candida albicans morphogenesis. Trends Microbiol7:333–338
    [Google Scholar]
  4. Buchler J. W. 1975; Static coordination chemistry of metalloporphyrins. In Porphyrins and Metalloporphyrins pp 157–224 Edited by Smith K. M.. Amsterdam: Elsevier;
    [Google Scholar]
  5. Casanova M, Cervera A, Gozalbo D., Martinez J. 1997; Hemin induces germ tube formation in Candida albicans . Infect Immun65:4360–4364
    [Google Scholar]
  6. Chu G, Katakura K, Zhang X, Yoshida T., Ikeda-Saito M. 1999; Heme degradation as catalyzed by a recombinant bacterial heme oxygenase (HmuO) from Corynebacterium diphtheriae . J Biol Chem274:21319–21325
    [Google Scholar]
  7. Dancis A, Roman D. G, Anderson G. J, Hinnebusch A. G., Klausner R. D. 1992; Ferric reductase of Saccharomyces cerevisiae : molecular characterization, role in iron uptake, and transcriptional control by iron. Proc Natl Acad Sci U S A89:3869–3873
    [Google Scholar]
  8. Eck R, Hundt S, Hartl A, Roemer E., Kunkel W. 1999; A multicopper oxidase gene from Candida albicans : cloning, characterization and disruption. Microbiology145:2415–2422
    [Google Scholar]
  9. Eide D. J. 2000; Metal ion transport in eukaryotic microorganisms: insights from Saccharomyces cerevisiae . Adv Microb Physiol43:1–38
    [Google Scholar]
  10. Emery T. 1987; Reductive mechanisms of iron assimilation. In Iron Transport in Microbes, Plants and Animals pp 235–250 Edited by Winkelmann G., van der Helm D., Neilands J. B.. Weinheim: VCH;
    [Google Scholar]
  11. Foster L. A. 2002; Utilization and cell-surface binding of hemin by Histoplasma capsulatum . Can J Microbiol48:437–442
    [Google Scholar]
  12. Galbraith R, Sassa S., Kappas A. 1985; Heme binding to murine erythroleukemia cells. Evidence for a heme receptor. J Biol Chem260:12198–12202
    [Google Scholar]
  13. Genco C., Dixon D. 2001; Emerging strategies in microbial haem capture. Mol Microbiol39:1–11
    [Google Scholar]
  14. Hammacott J. E, Williams P. H., Cashmore A. M. 2000; Candida albicans CFL1 encodes a functional ferric reductase activity that can rescue a Saccharomyces cerevisiae fre1 mutant. Microbiology146:869–876
    [Google Scholar]
  15. Heymann P, Ernst J. F., Winkelmann G. 1999; Identification of a fungal triacetylfusarinine C siderophore transport gene ( TAF1 ) in Saccharomyces cerevisiae as a member of the major facilitator superfamily. Biometals12:301–306
    [Google Scholar]
  16. Heymann P, Ernst J. F., Winkelmann G. 2000; A gene of the major facilitator superfamily encodes a transporter for enterobactin (Enb1p) in Saccharomyces cerevisiae . Biometals13:65–72
    [Google Scholar]
  17. Heymann P, Gerads M, Schaller M, Dromer F, Winkelmann G., Ernst J. 2002; The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion. Infect Immun70:5246–5255
    [Google Scholar]
  18. Holzberg M., Artis W. M. 1983; Hydroxamate siderophore production by opportunistic and systemic fungal pathogens. Infect Immun40:1134–1139
    [Google Scholar]
  19. Howard D. H. 1999; Acquisition, transport, and storage of iron by pathogenic fungi. Clin Microbiol Rev12:394–404
    [Google Scholar]
  20. Hu C, Bai C, Zheng X, Wang Y., Wang Y. 2002; Characterization and functional analysis of the siderophore-iron transporter CaArn1p in Candida albicans . J Biol Chem277:30598–30605
    [Google Scholar]
  21. Ismail A, Bedell G. W., Lupan D. M. 1985; Siderophore production by the pathogenic yeast, Candida albicans . Biochem Biophys Res Commun130:885–891
    [Google Scholar]
  22. Knight S. A, Lesuisse E, Stearman R, Klausner R. D., Dancis A. 2002; Reductive iron uptake by Candida albicans : role of copper, iron and the TUP1 regulator. Microbiology148:29–40
    [Google Scholar]
  23. Kohrer K., Domdey H. 1991; Preparation of high molecular weight RNA. Methods Enzymol194:398–405
    [Google Scholar]
  24. Laine L., Bonacini M. 1994; Esophageal disease in human immunodeficiency virus infection. Arch Intern Med154:1577–1582
    [Google Scholar]
  25. Leng P, Lee P. R, Wu H., Brown A. J. 2001; Efg1, a morphogenetic regulator in Candida albicans , is a sequence-specific DNA binding protein. J Bacteriol183:4090–4093
    [Google Scholar]
  26. Lesuisse E, Raguzzi F., Crichton R. R. 1987; Iron uptake by the yeast Saccharomyces cerevisiae : involvement of a reduction step. J Gen Microbiol133:3229–3236
    [Google Scholar]
  27. Lesuisse E, Simon-Casteras M., Labbe P. 1998; Siderophore-mediated iron uptake in Saccharomyces cerevisiae : the SIT1 gene encodes a ferrioxamine B permease that belongs to the major facilitator superfamily. Microbiology144:3455–3462
    [Google Scholar]
  28. Lesuisse E, Knight S. A, Camadro J. M., Dancis A. 2002; Siderophore uptake by Candida albicans : effect of serum treatment and comparison with Saccharomyces cerevisiae . Yeast19:329–340
    [Google Scholar]
  29. Liu H. 2001; Transcriptional control of dimorphism in Candida albicans . Curr Opin Microbiol4:728–735
    [Google Scholar]
  30. Manns J. M, Mosser D. M., Buckley H. R. 1994; Production of a hemolytic factor by Candida albicans . Infect Immun62:5154–5156
    [Google Scholar]
  31. Moors M. A, Stull T. L, Blank K. J, Buckley H. R., Mosser D. M. 1992; A role for complement receptor-like molecules in iron acquisition by Candida albicans . J Exp Med175:1643–1651
    [Google Scholar]
  32. Morrissey J. A, Williams P. H., Cashmore A. M. 1996; Candida albicans has a cell-associated ferric-reductase activity which is regulated in response to levels of iron and copper. Microbiology142:485–492
    [Google Scholar]
  33. Morse D., Choi A. M. 2002; Heme oxygenase-1: ‘the emerging molecule’ has arrived. Am J Respir Cell Mol Biol27:8–16
    [Google Scholar]
  34. Payne S. M. 1993; Iron acquisition in microbial pathogenesis. Trends Microbiol1:66–69
    [Google Scholar]
  35. Poss K., Tonegawa S. 1997; Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci U S A94:10919–10924
    [Google Scholar]
  36. Ramanan N., Wang Y. 2000; A high-affinity iron permease essential for Candida albicans virulence. Science288:1062–1064
    [Google Scholar]
  37. Ratledge C., Dover L. G. 2000; Iron metabolism in pathogenic bacteria. Annu Rev Microbiol54:881–941
    [Google Scholar]
  38. Rex J. H, Rinaldi M. G., Pfaller M. A. 1995; Resistance of Candida species to fluconazole. Antimicrob Agents Chemother39:1–8
    [Google Scholar]
  39. Sambrook J, Fritsch E. F., Maniatis T. 1989; Molecular Cloning: a Laboratory Manual , 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  40. Schuller D. J, Wilks A, Ortiz de Montellano P. R., Poulos T. L. 1999; Crystal structure of human heme oxygenase-1. Nat Struct Biol6:860–867
    [Google Scholar]
  41. Schuller D. J, Zhu W, Stojiljkovic I, Wilks A., Poulos T. L. 2001; Crystal structure of heme oxygenase from the gram-negative pathogen Neisseria meningitidis and a comparison with mammalian heme oxygenase-1. Biochemistry40:11552–11558
    [Google Scholar]
  42. Stearman R, Yuan D. S, Yamaguchi-Iwai Y, Klausner R. D., Dancis A. 1996; A permease–oxidase complex involved in high-affinity iron uptake in yeast. Science271:1552–1557
    [Google Scholar]
  43. Stoldt V. R, Sonneborn A, Leuker C. E., Ernst J. F. 1997; Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans , is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. EMBO J16:1982–1991
    [Google Scholar]
  44. Sweet S. P., Douglas L. J. 1991; Effect of iron concentration on siderophore synthesis and pigment production by Candida albicans . FEMS Microbiol Lett64:87–91
    [Google Scholar]
  45. Van Ho A, Ward D. M., Kaplan J. 2002; Transition metal transport in yeast. Annu Rev Microbiol56:237–261
    [Google Scholar]
  46. Weissman Z, Shemer R., Kornitzer D. 2002; Deletion of the copper transporter CaCCC2 reveals two distinct pathways for iron acquisition in Candida albicans . Mol Microbiol44:1551–1560
    [Google Scholar]
  47. Whiteway M. 2000; Transcriptional control of cell type and morphogenesis in Candida albicans . Curr Opin Microbiol3:582–588
    [Google Scholar]
  48. Wilson R, Davis D., Mitchell A. 1999; Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J Bacteriol181:1868–1874
    [Google Scholar]
  49. Yun C. W, Tiedeman J. S, Moore R. E., Philpott C. C. 2000; Siderophore-iron uptake in Saccharomyces cerevisiae . Identification of ferrichrome and fusarinine transporters. J Biol Chem275:16354–16359
    [Google Scholar]
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