Skip to main content

Metal Acquisition and Homeostasis in Fungi

Abstract

Transition metals, particularly iron, zinc and copper, have multiple biological roles and are essential elements in biological processes. Among other micronutrients, these metals are frequently available to cells in only limited amounts, thus organisms have evolved highly regulated mechanisms to cope and to compete with their scarcity. The homeostasis of such metals within the animal hosts requires the integration of multiple signals producing depleted environments that restrict the growth of microorganisms, acting as a barrier to infection. As the hosts sequester the necessary transition metals from invading pathogens, some, as is the case of fungi, have evolved elaborate mechanisms to allow their survival and development to establish infection. Metalloregulatory factors allow fungal cells to sense and to adapt to the scarce metal availability in the environment, such as in host tissues. Here we review recent advances in the identification and function of molecules that drive the acquisition and homeostasis of iron, copper and zinc in pathogenic fungi.

This is a preview of subscription content, access via your institution.

Fig. 1

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. • Almeida RS, Wilson D, Hube B. Candida albicans iron acquisition within the host. FEMS Yeast Res. 2009;9:1000–12. This article reviews the iron sources used by C. albicans during infection in the human host, that are xenosiderophores, hemoglobin, transferrin and ferritin.

    PubMed  Article  CAS  Google Scholar 

  2. • Nairz M, Schroll A, Sonnweber T, Weiss G. The struggle for iron – a metal at the host-pathogen interface. Cell Microbiol. 2010;12:1691–702. This article reviews the iron functions at the host–pathogen interface since mammalian and microbial cells have an essential demand for the metal. Microbial iron acquisition pathways are attractive targets for the development of new antimicrobial drugs.

    PubMed  Article  CAS  Google Scholar 

  3. Theurl I, Fritsche G, Ludwiczek S, et al. The macrophage: a cellular factory at the interphase between iron and immunity for the control of infections. Biometals. 2005;18:359–67.

    PubMed  Article  CAS  Google Scholar 

  4. Ibrahim AS, Gebermariam T, Fu Y, et al. The iron chelator deferasirox protects mice from mucormycosis through iron starvation. J Clin Invest. 2007;117:2649–57.

    PubMed  Article  CAS  Google Scholar 

  5. Kaplan CD, Kaplan J. Iron acquisition and transcriptional regulation. Chem Rev. 2009;109:4536–52.

    PubMed  Article  CAS  Google Scholar 

  6. Kim BE, Nevitt T, Thiele DJ. Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol. 2008;4:176–85.

    PubMed  Article  CAS  Google Scholar 

  7. Lulloff SJ, Hahn BL, Sohnle PG. Fungal susceptibility to zinc deprivation. J Lab Clin Med. 2004;144:208–14.

    PubMed  Article  CAS  Google Scholar 

  8. Barluzzi R, Saleppico S, Nocentini A, et al. Iron overload exacerbates experimental meningoencephalitis by Cryptococcus neoformans. J Neuroimmunol. 2002;132:140–6.

    PubMed  Article  CAS  Google Scholar 

  9. Parente AF, Bailão AM, Borges CL, et al. Proteomic analysis reveals that iron availability alters the metabolic status of the pathogenic fungus Paracoccidioides brasiliensis. PLoS One. 2011;6:e22810.

    PubMed  Article  CAS  Google Scholar 

  10. Nevitt T. War-Fe-re: iron at the core of fungal virulence and host immunity. Biometals. 2011;24:547–58.

    PubMed  Article  CAS  Google Scholar 

  11. Al-Sheikh H. Effect of lactoferrin and iron on the growth of human pathogenic Candida species. Pak J Biol Sci. 2009;12:91–4.

    PubMed  Article  CAS  Google Scholar 

  12. Weinberg ED. Iron loading and disease surveillance. Emerg Infect Dis. 1999;5:346–52.

    PubMed  Article  CAS  Google Scholar 

  13. Weiss G. Modification of iron regulation by the inflammatory response. Best Pract Res Clin Haematol. 2005;18:183–201.

    PubMed  Article  CAS  Google Scholar 

  14. Winters MS, Chan Q, Caruso JA, Deepe Jr GS. Metallomic analysis of macrophages infected with Histoplasma capsulatum reveals a fundamental role for zinc in host defenses. J Infect Dis. 2010;202:1136–45.

    PubMed  Article  CAS  Google Scholar 

  15. Byrd TF, Horwitz MA. Regulation of transferrin receptor expression and ferritin content in human mononuclear phagocytes. Coordinate upregulation by iron transferrin and downregulation by interferon gamma. J Clin Invest. 1993;91:969–76.

    PubMed  Article  CAS  Google Scholar 

  16. Bailão AM, Schrank A, Borges CL, et al. Differential gene expression by Paracoccidioides brasiliensis in host interaction conditions: representational difference analysis identifies candidate genes associated with fungal pathogenesis. Microbes Infect. 2006;8:2686–97.

    PubMed  Article  Google Scholar 

  17. Samanovic MI, Ding C, Thiele DJ, Darwin KH. Copper in microbial pathogenesis: meddling with the metal. Cell Host Microbe. 2012;11:106–15.

    PubMed  Article  CAS  Google Scholar 

  18. Walton FJ, Idnurm A, Heitman J. Novel gene functions required for melanization of the human pathogen Cryptococcus neoformans. Mol Microbiol. 2005;57:1381–96.

    PubMed  Article  CAS  Google Scholar 

  19. Beisel WR. Herman Award Lecture, 1995: infection-induced malnutrition – from cholera to cytokines. Am J Clin Nutr. 1995;62:813–9.

    PubMed  CAS  Google Scholar 

  20. Sohnle PG, Collins-Lech C, Wiessner JH. The zinc-reversible antimicrobial activity of neutrophil lysates and abscess fluid supernatants. J Infect Dis. 1991;164:137–42.

    PubMed  Article  CAS  Google Scholar 

  21. Haas H, Eisendle M, Turgeon BG. Siderophores in fungal physiology and virulence. Annu Rev Phytopathol. 2008;46:149–87.

    PubMed  Article  CAS  Google Scholar 

  22. Harrington JM, Crumbliss AL. The redox hypothesis in siderophore-mediated iron uptake. Biometals. 2009;22:679–89.

    PubMed  Article  CAS  Google Scholar 

  23. Renshaw JC, Robson GD, Trinci APJ, et al. Fungal siderophores: structures, functions and applications. Mycol Res. 2002;106:1123–42.

    Article  CAS  Google Scholar 

  24. Jacobson ES, Petro MJ. Extracellular iron chelation in Cryptococcus neoformans. J Med Vet Mycol. 1987;25:415–8.

    PubMed  Article  CAS  Google Scholar 

  25. Jeeves RE, Mason RP, Woodacre A, Cashmore AM. Ferric reductase genes involved in high-affinity iron uptake are differentially regulated in yeast and hyphae of Candida albicans. Yeast. 2011;28:629–44.

    PubMed  Article  CAS  Google Scholar 

  26. • Ziegler L, Terzulli A, Gaur R, et al. Functional characterization of the ferroxidase, permease high-affinity iron transport complex from Candida albicans. Mol Microbiol. 2011;81:473–85. This article demonstrates that Fe trafficking in C. albicans involves a complex Fet34-Ftr1 using S. cerevisiae as host for the functional expression of the C. albicans Fe-uptake proteins.

    PubMed  Article  CAS  Google Scholar 

  27. Heymann P, Gerads M, Schaller M, et al. The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion. Infect Immun. 2002;70:5246–55.

    PubMed  Article  CAS  Google Scholar 

  28. Hu CJ, Bai C, Zheng XD, et al. Characterization and functional analysis of the siderophore-iron transporter CaArn1p in Candida albicans. J Biol Chem. 2002;277:30598–605.

    PubMed  Article  CAS  Google Scholar 

  29. Zarnowski R, Cooper KG, Brunold LS, et al. Histoplasma capsulatum secreted gamma-glutamyltransferase reduces iron by generating an efficient ferric reductant. Mol Microbiol. 2008;70:352–68.

    PubMed  Article  CAS  Google Scholar 

  30. Timmerman MM, Woods JP. Ferric reduction is a potential iron acquisition mechanism for Histoplasma capsulatum. Infect Immun. 1999;67:6403–8.

    PubMed  CAS  Google Scholar 

  31. Hwang LH, Mayfield JA, Rine J, Sil A. Histoplasma requires SID1, a member of an iron-regulated siderophore gene cluster, for host colonization. PLoS Pathog. 2008;4:e1000044.

    PubMed  Article  Google Scholar 

  32. Hilty J, George Smulian A, Newman SL. Histoplasma capsulatum utilizes siderophores for intracellular iron acquisition in macrophages. Med Mycol. 2011;49:633–42.

    PubMed  CAS  Google Scholar 

  33. Howard DH, Rafie R, Tiwari A, Faull KF. Hydroxamate siderophores of Histoplasma capsulatum. Infect Immun. 2000;68:2338–43.

    PubMed  Article  CAS  Google Scholar 

  34. Timmerman MM, Woods JP. Potential role for extracellular glutathione-dependent ferric reductase in utilization of environmental and host ferric compounds by Histoplasma capsulatum. Infect Immun. 2001;69:7671–8.

    PubMed  Article  CAS  Google Scholar 

  35. Blatzer M, Binder U, Haas H. The metalloreductase FreB is involved in adaptation of Aspergillus fumigatus to iron starvation. Fungal Genet Biol. 2011;48:1027–33.

    PubMed  Article  CAS  Google Scholar 

  36. Charlang G, Ng B, Horowitz NH, Horowitz RM. Cellular and extracellular siderophores of Aspergillus nidulans and Penicillium chrysogenum. Mol Cell Biol. 1981;1:94–100.

    PubMed  CAS  Google Scholar 

  37. Schrettl M, Bignell E, Kragl C, et al. Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence. J Exp Med. 2004;200:1213–9.

    PubMed  Article  CAS  Google Scholar 

  38. Eisendle M, Schrettl M, Kragl C, et al. The intracellular siderophore ferricrocin is involved in iron storage, oxidative-stress resistance, germination, and sexual development in Aspergillus nidulans. Eukaryot Cell. 2006;5:1596–603.

    PubMed  Article  CAS  Google Scholar 

  39. Haas H. Molecular genetics of fungal siderophore biosynthesis and uptake: the role of siderophores in iron uptake and storage. Appl Microbiol Biotechnol. 2003;62:316–30.

    PubMed  Article  CAS  Google Scholar 

  40. Kragl C, Schrettl M, Abt B, et al. EstB-mediated hydrolysis of the siderophore triacetylfusarinine C optimizes iron uptake of Aspergillus fumigatus. Eukaryot Cell. 2007;6:1278–85.

    PubMed  Article  CAS  Google Scholar 

  41. • Haas H. Iron – a key nexus in the virulence of Aspergillus fumigatus. Front Microbiol. 2012;3:28. This article reviews iron homeostasis and its participation in virulence in Aspergillus genus. The knowledge of the iron handling between host and fungus might improve therapy and diagnosis of fungal infections.

    PubMed  Google Scholar 

  42. Jacobson ES, Goodner AP, Nyhus KJ. Ferrous iron uptake in Cryptococcus neoformans. Infect Immun. 1998;66:4169–75.

    PubMed  CAS  Google Scholar 

  43. Jung WH, Kronstad JW. Iron and fungal pathogenesis: a case study with Cryptococcus neoformans. Cell Microbiol. 2008;10:277–84.

    PubMed  Article  CAS  Google Scholar 

  44. Jung WH, Hu G, Kuo W, Kronstad JW. Role of ferroxidases in iron uptake and virulence of Cryptococcus neoformans. Eukaryot Cell. 2009;8:1511–20.

    PubMed  Article  CAS  Google Scholar 

  45. Silva MG, Schrank A, Bailão EF, et al. The homeostasis of iron, copper, and zinc in Paracoccidioides brasiliensis, Cryptococcus neoformans var. grubii, and Cryptococcus gattii: a comparative analysis. Front Microbiol. 2011;2:49.

    PubMed  CAS  Google Scholar 

  46. Zarnowski R, Woods JP. Glutathione-dependent extracellular ferric reductase activities in dimorphic zoopathogenic fungi. Microbiology. 2005;151:2233–40.

    PubMed  Article  CAS  Google Scholar 

  47. Castaneda E, Brummer E, Perlman AM, et al. A culture medium for Paracoccidioides brasiliensis with high plating efficiency, and the effect of siderophores. J Med Vet Mycol. 1988;26:351–8.

    PubMed  Article  CAS  Google Scholar 

  48. Knight SA, Labbe S, Kwon LF, et al. A widespread transposable element masks expression of a yeast copper transport gene. Genes Dev. 1996;10:1917–29.

    PubMed  Article  CAS  Google Scholar 

  49. Hammacott JE, Williams PH, Cashmore AM. Candida albicans CFL1 encodes a functional ferric reductase activity that can rescue a Saccharomyces cerevisiae fre1 mutant. Microbiology. 2000;146(Pt 4):869–76.

    PubMed  CAS  Google Scholar 

  50. Marvin ME, Williams PH, Cashmore AM. The Candida albicans CTR1 gene encodes a functional copper transporter. Microbiology. 2003;149:1461–74.

    PubMed  Article  CAS  Google Scholar 

  51. Williamson PR. Biochemical and molecular characterization of the diphenol oxidase of Cryptococcus neoformans: identification as a laccase. J Bacteriol. 1994;176:656–64.

    PubMed  CAS  Google Scholar 

  52. Nyhus KJ, Jacobson ES. Genetic and physiologic characterization of ferric/cupric reductase constitutive mutants of Cryptococcus neoformans. Infect Immun. 1999;67:2357–65.

    PubMed  CAS  Google Scholar 

  53. • Ding C, Yin J, Tovar EM, et al. The copper regulon of the human fungal pathogen Cryptococcus neoformans H99. Mol Microbiol. 2011;81:1560–76. This article describes a new C. neoformans Cu transporter, Ctr1, and some targets of the metalloregulatory transcription factor Cuf1.

    PubMed  Article  CAS  Google Scholar 

  54. Zhao H, Eide D. The ZRT2 gene encodes the low affinity zinc transporter in Saccharomyces cerevisiae. J Biol Chem. 1996;271:23203–10.

    PubMed  Article  CAS  Google Scholar 

  55. Zhao H, Eide D. The yeast ZRT1 gene encodes the zinc transporter protein of a high-affinity uptake system induced by zinc limitation. Proc Natl Acad Sci U S A. 1996;93:2454–8.

    PubMed  Article  CAS  Google Scholar 

  56. Amich J, Vicentefranqueira R, Leal F, Calera JA. Aspergillus fumigatus survival in alkaline and extreme zinc-limiting environments relies on the induction of a zinc homeostasis system encoded by the zrfC and aspf2 genes. Eukaryot Cell. 2009;9:424–37.

    PubMed  Article  Google Scholar 

  57. Amich J, Leal F, Calera JA. Repression of the acid ZrfA/ZrfB zinc-uptake system of Aspergillus fumigatus mediated by PacC under neutral, zinc-limiting conditions. Int Microbiol. 2009;12:39–47.

    PubMed  CAS  Google Scholar 

  58. Vicentefranqueira R, Moreno MA, Leal F, Calera JA. The zrfA and zrfB genes of Aspergillus fumigatus encode the zinc transporter proteins of a zinc uptake system induced in an acid, zinc-depleted environment. Eukaryot Cell. 2005;4:837–48.

    PubMed  Article  CAS  Google Scholar 

  59. Weissman Z, Kornitzer D. A family of Candida cell surface haem-binding proteins involved in haemin and haemoglobin-iron utilization. Mol Microbiol. 2004;53:1209–20.

    PubMed  Article  CAS  Google Scholar 

  60. Santos R, Buisson N, Knight S, et al. Haemin uptake and use as an iron source by Candida albicans: role of CaHMX1-encoded haem oxygenase. Microbiology. 2003;149:579–88.

    PubMed  Article  CAS  Google Scholar 

  61. Knight SA, Vilaire G, Lesuisse E, Dancis A. Iron acquisition from transferrin by Candida albicans depends on the reductive pathway. Infect Immun. 2005;73:5482–92.

    PubMed  Article  CAS  Google Scholar 

  62. Rutherford JC, Bird AJ. Metal-responsive transcription factors that regulate iron, zinc, and copper homeostasis in eukaryotic cells. Eukaryot Cell. 2004;3:1–13.

    PubMed  Article  CAS  Google Scholar 

  63. Scazzocchio C. The fungal GATA factors. Curr Opin Microbiol. 2000;3:126–31.

    PubMed  Article  CAS  Google Scholar 

  64. Lan CY, Rodarte G, Murillo LA, et al. Regulatory networks affected by iron availability in Candida albicans. Mol Microbiol. 2004;53:1451–69.

    PubMed  Article  CAS  Google Scholar 

  65. Hsu PC, Yang CY, Lan CY. Candida albicans Hap43 is a repressor induced under low-iron conditions and is essential for iron-responsive transcriptional regulation and virulence. Eukaryot Cell. 2011;10:207–25.

    PubMed  Article  CAS  Google Scholar 

  66. • Singh RP, Prasad HK, Sinha I, et al. Cap2-HAP complex is a critical transcriptional regulator that has dual but contrasting roles in regulation of iron homeostasis in Candida albicans. J Biol Chem. 2011;286:25154–70. This article describes the roles performed by Cap2 under iron limiting conditions: activation of genes in iron uptake pathways and repression of iron-utilizing and iron-storage genes.

    PubMed  Article  CAS  Google Scholar 

  67. Homann OR, Dea J, Noble SM, Johnson AD. A phenotypic profile of the Candida albicans regulatory network. PLoS Genet. 2009;5:e1000783.

    PubMed  Article  Google Scholar 

  68. Baek YU, Li M, Davis DA. Candida albicans ferric reductases are differentially regulated in response to distinct forms of iron limitation by the Rim101 and CBF transcription factors. Eukaryot Cell. 2008;7:1168–79.

    PubMed  Article  CAS  Google Scholar 

  69. Chao LY, Marletta MA, Rine J. Sre1, an iron-modulated GATA DNA-binding protein of iron-uptake genes in the fungal pathogen Histoplasma capsulatum. Biochemistry. 2008;47:7274–83.

    PubMed  Article  CAS  Google Scholar 

  70. Hwang LH, Seth E, Gilmore SA, Sil A. SRE1 regulates iron-dependent and -independent pathways in the fungal pathogen Histoplasma capsulatum. Eukaryot Cell. 2012;11:16–25.

    PubMed  Article  CAS  Google Scholar 

  71. Gauthier GM, Sullivan TD, Gallardo SS, et al. SREB, a GATA transcription factor that directs disparate fates in Blastomyces dermatitidis including morphogenesis and siderophore biosynthesis. PLoS Pathog. 2010;6:e1000846.

    PubMed  Article  Google Scholar 

  72. Schrettl M, Kim HS, Eisendle M, et al. SreA-mediated iron regulation in Aspergillus fumigatus. Mol Microbiol. 2008;70:27–43.

    PubMed  Article  CAS  Google Scholar 

  73. • Schrettl M, Beckmann N, Varga J, et al. HapX-mediated adaption to iron starvation is crucial for virulence of Aspergillus fumigatus. PLoS Pathog. 2010;6:e1001124. This article describes the functions of transcriptional regulator HapX of A. fumigatus, which is important to fungus adaptation in iron starvation conditions and is crucial for virulence in a murine model of infection.

    PubMed  Article  Google Scholar 

  74. Liu H, Gravelat FN, Chiang LY, et al. Aspergillus fumigatus AcuM regulates both iron acquisition and gluconeogenesis. Mol Microbiol. 2010;78:1038–54.

    PubMed  Article  CAS  Google Scholar 

  75. Jung WH, Sham A, White R, Kronstad JW. Iron regulation of the major virulence factors in the AIDS-associated pathogen Cryptococcus neoformans. PLoS Biol. 2006;4:e410.

    PubMed  Article  Google Scholar 

  76. Jung WH, Sham A, Lian T, et al. Iron source preference and regulation of iron uptake in Cryptococcus neoformans. PLoS Pathog. 2008;4:e45.

    PubMed  Article  Google Scholar 

  77. Jung WH, Kronstad JW. Iron influences the abundance of the iron regulatory protein Cir1 in the fungal pathogen Cryptococcus neoformans. FEBS Lett. 2011;585:3342–7.

    PubMed  Article  CAS  Google Scholar 

  78. Jung WH, Saikia S, Hu G, et al. HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans. PLoS Pathog. 2010;6:e1001209.

    PubMed  Article  Google Scholar 

  79. Waterman SR, Hacham M, Hu G, et al. Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans. J Clin Invest. 2007;117:794–802.

    PubMed  Article  CAS  Google Scholar 

  80. Woodacre A, Mason RP, Jeeves RE, Cashmore AM. Copper-dependent transcriptional regulation by Candida albicans Mac1p. Microbiology. 2008;154:1502–12.

    PubMed  Article  CAS  Google Scholar 

  81. Dantas SF, Vieira de Rezende TC, Bailão AM, et al. Identification and characterization of antigenic proteins potentially expressed during the infectious process of Paracoccidioides brasiliensis. Microbes Infect. 2009;11:895–903.

    PubMed  Article  CAS  Google Scholar 

  82. Bailão AM, Nogueira SV. Rondon Caixeta Bonfim SM, et al. Comparative transcriptome analysis of Paracoccidioides brasiliensis during in vitro adhesion to type I collagen and fibronectin: identification of potential adhesins. Res Microbiol. 2012;163:182–91.

    PubMed  Article  Google Scholar 

  83. Kim MJ, Kil M, Jung JH, Kim J. Roles of zinc-responsive transcription factor Csr1 in filamentous growth of the pathogenic yeast Candida albicans. J Microbiol Biotechnol. 2008;18:242–7.

    PubMed  CAS  Google Scholar 

  84. Nobile CJ, Nett JE, Hernday AD, et al. Biofilm matrix regulation by Candida albicans Zap1. PLoS Biol. 2009;7:e1000133.

    PubMed  Article  Google Scholar 

  85. Finkel JS, Xu W, Huang D, et al. Portrait of Candida albicans adherence regulators. PLoS Pathog. 2012;8:e1002525.

    PubMed  Article  CAS  Google Scholar 

  86. Ganguly S, Bishop AC, Xu W, et al. Zap1 control of cell-cell signaling in Candida albicans biofilms. Eukaryot Cell. 2011;10:1448–54.

    PubMed  Article  CAS  Google Scholar 

  87. Moreno MA, Ibrahim-Granet O, Vicentefranqueira R, et al. The regulation of zinc homeostasis by the ZafA transcriptional activator is essential for Aspergillus fumigatus virulence. Mol Microbiol. 2007;64:1182–97.

    PubMed  Article  CAS  Google Scholar 

  88. Kehl-Fie TE, Skaar EP. Nutritional immunity beyond iron: a role for manganese and zinc. Curr Opin Chem Biol. 2010;14:218–24.

    PubMed  Article  CAS  Google Scholar 

  89. Weinberg ED. Iron availability and infection. Biochim Biophys Acta. 2009;1790:600–5.

    PubMed  Article  CAS  Google Scholar 

  90. Ramanan N, Wang Y. A high-affinity iron permease essential for Candida albicans virulence. Science. 2000;288:1062–4.

    PubMed  Article  CAS  Google Scholar 

  91. Liang Y, Wei D, Wang H, et al. Role of Candida albicans Aft2p transcription factor in ferric reductase activity, morphogenesis and virulence. Microbiology. 2010;156:2912–9.

    PubMed  Article  CAS  Google Scholar 

  92. Chen C, Pande K, French SD, et al. An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis. Cell Host Microbe. 2011;10:118–35.

    PubMed  Article  CAS  Google Scholar 

  93. • Navarathna DH, Roberts DD. Candida albicans heme oxygenase and its product CO contribute to pathogenesis of candidemia and alter systemic chemokine and cytokine expression. Free Radic Biol Med. 2010;49:1561–73. This article describes the heme oxygenase Hmx1 as a virulence factor in C. albicans. The authors observed that mutants lacking hmx1 gene were not affected during initial kidney colonization, but Hmx1 absence clearly affects infection progression.

    PubMed  Article  CAS  Google Scholar 

  94. Hissen AH, Wan AN, Warwas ML, et al. The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence. Infect Immun. 2005;73:5493–503.

    PubMed  Article  CAS  Google Scholar 

  95. Schrettl M, Bignell E, Kragl C, et al. Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. PLoS Pathog. 2007;3:1195–207.

    PubMed  Article  CAS  Google Scholar 

  96. Cox GM, Harrison TS, McDade HC, et al. Superoxide dismutase influences the virulence of Cryptococcus neoformans by affecting growth within macrophages. Infect Immun. 2003;71:173–80.

    PubMed  Article  CAS  Google Scholar 

  97. Chun CD, Madhani HD. Ctr2 links copper homeostasis to polysaccharide capsule formation and phagocytosis inhibition in the human fungal pathogen Cryptococcus neoformans. PloS One. 2010;5.

  98. Zhu X, Williamson PR. A CLC-type chloride channel gene is required for laccase activity and virulence in Cryptococcus neoformans. Mol Microbiol. 2003;50:1271–81.

    PubMed  Article  CAS  Google Scholar 

  99. Bignell E, Negrete-Urtasun S, Calcagno AM, et al. The Aspergillus pH-responsive transcription factor PacC regulates virulence. Mol Microbiol. 2005;55:1072–84.

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

Work at Universidade Federal de Goiás and Universidade Federal do Rio Grande do Sul was supported by grants from Financiadora de Estudos e Projetos (FINEP- 01.07.0552.00) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-558923/2009-7 and 478591/2010-1). E.F.L.C.B. and M.G.S.B. are supported by doctoral fellowships from Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). A.F.A.P. and L.K. are supported by postdoctoral fellowships from CAPES. We apologize to colleagues whose work we were not able to cite due to space limitations.

Disclosure

E.F. Bailão: grants from Capes, CNPq and FINEP; A.F.A. Parente: grants from CNPq, CAPES and FINEP; J.A. Parente: none; M. Garcia Silva-Bailão: grant from CAPES; K. Castro: grants from FINEP and CNPq; L. Kmetzsch: grants from CAPES, CNPq and FINEP; C. Staats: grants from CNPq and FINEP; A. Schrank: grants from CNPq and FINEP; M. Vainstein: grants from CNPq and FINEP; C. Borges: grants from CNPq and FINEP; A. Bailão: grant from CNPq; C.M. Soares: grants from FINEP and CNPq.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Célia Maria de Almeida Soares.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bailão, E.F.L.C., Parente, A.F.A., Parente, J.A. et al. Metal Acquisition and Homeostasis in Fungi. Curr Fungal Infect Rep 6, 257–266 (2012). https://doi.org/10.1007/s12281-012-0108-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12281-012-0108-8

Keywords

  • Iron
  • Copper
  • Zinc
  • Fungal pathogens