1887

Microbiology Society logo

Volume 149, Issue 3

Haemin uptake and use as an iron source by : role of -encoded haem oxygenase Free

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.

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): BPS, bathophenanthroline disulfonic acid
SGM
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.26108-0
2003-03-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/micro/149/3/mic149579.html?itemId=/content/journal/micro/10.1099/mic.0.26108-0&mimeType=html&fmt=ahah

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 Chem 276:43049–43055
     [Google Scholar]
  2. Braun B. R., Johnson A. D. 1997; Control of filament formation in Candida albicans by the transcriptional repressor TUP1 . Science 277:105–109
     [Google Scholar]
  3. Brown A. J., Gow N. A. 1999; Regulatory networks controlling Candida albicans morphogenesis. Trends Microbiol 7:333–338
     [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 Immun 65:4360–4364
     [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 Chem 274:21319–21325
     [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 A 89:3869–3873
     [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. Microbiology 145:2415–2422
     [Google Scholar]
  9. Eide D. J. 2000; Metal ion transport in eukaryotic microorganisms: insights from Saccharomyces cerevisiae . Adv Microb Physiol 43:1–38
     [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 Microbiol 48:437–442
     [Google Scholar]
  12. Galbraith R, Sassa S., Kappas A. 1985; Heme binding to murine erythroleukemia cells. Evidence for a heme receptor. J Biol Chem 260:12198–12202
     [Google Scholar]
  13. Genco C., Dixon D. 2001; Emerging strategies in microbial haem capture. Mol Microbiol 39:1–11
     [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. Microbiology 146:869–876
     [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. Biometals 12:301–306
     [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 . Biometals 13:65–72
     [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 Immun 70:5246–5255
     [Google Scholar]
  18. Holzberg M., Artis W. M. 1983; Hydroxamate siderophore production by opportunistic and systemic fungal pathogens. Infect Immun 40:1134–1139
     [Google Scholar]
  19. Howard D. H. 1999; Acquisition, transport, and storage of iron by pathogenic fungi. Clin Microbiol Rev 12:394–404
     [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 Chem 277:30598–30605
     [Google Scholar]
  21. Ismail A, Bedell G. W., Lupan D. M. 1985; Siderophore production by the pathogenic yeast, Candida albicans . Biochem Biophys Res Commun 130:885–891
     [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. Microbiology 148:29–40
     [Google Scholar]
  23. Kohrer K., Domdey H. 1991; Preparation of high molecular weight RNA. Methods Enzymol 194:398–405
     [Google Scholar]
  24. Laine L., Bonacini M. 1994; Esophageal disease in human immunodeficiency virus infection. Arch Intern Med 154:1577–1582
     [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 Bacteriol 183:4090–4093
     [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 Microbiol 133:3229–3236
     [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. Microbiology 144:3455–3462
     [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 . Yeast 19:329–340
     [Google Scholar]
  29. Liu H. 2001; Transcriptional control of dimorphism in Candida albicans . Curr Opin Microbiol 4:728–735
     [Google Scholar]
  30. Manns J. M, Mosser D. M., Buckley H. R. 1994; Production of a hemolytic factor by Candida albicans . Infect Immun 62:5154–5156
     [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 Med 175:1643–1651
     [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. Microbiology 142:485–492
     [Google Scholar]
  33. Morse D., Choi A. M. 2002; Heme oxygenase-1: ‘the emerging molecule’ has arrived. Am J Respir Cell Mol Biol 27:8–16
     [Google Scholar]
  34. Payne S. M. 1993; Iron acquisition in microbial pathogenesis. Trends Microbiol 1:66–69
     [Google Scholar]
  35. Poss K., Tonegawa S. 1997; Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci U S A 94:10919–10924
     [Google Scholar]
  36. Ramanan N., Wang Y. 2000; A high-affinity iron permease essential for Candida albicans virulence. Science 288:1062–1064
     [Google Scholar]
  37. Ratledge C., Dover L. G. 2000; Iron metabolism in pathogenic bacteria. Annu Rev Microbiol 54:881–941
     [Google Scholar]
  38. Rex J. H, Rinaldi M. G., Pfaller M. A. 1995; Resistance of Candida species to fluconazole. Antimicrob Agents Chemother 39:1–8
     [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 Biol 6:860–867
     [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. Biochemistry 40:11552–11558
     [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. Science 271:1552–1557
     [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 J 16:1982–1991
     [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 Lett 64:87–91
     [Google Scholar]
  45. Van Ho A, Ward D. M., Kaplan J. 2002; Transition metal transport in yeast. Annu Rev Microbiol 56:237–261
     [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 Microbiol 44:1551–1560
     [Google Scholar]
  47. Whiteway M. 2000; Transcriptional control of cell type and morphogenesis in Candida albicans . Curr Opin Microbiol 3:582–588
     [Google Scholar]
  48. Wilson R, Davis D., Mitchell A. 1999; Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions. J Bacteriol 181:1868–1874
     [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 Chem 275:16354–16359
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.26108-0
Loading
Haemin uptake and use as an iron source by Candida albicans: role of CaHMX1-encoded haem oxygenase
Microbiology 149, 579 (2003); https://doi.org/10.1099/mic.0.26108-0
/content/journal/micro/10.1099/mic.0.26108-0
/content/journal/micro/10.1099/mic.0.26108-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error