The high affinity iron permease is a key virulence factor required for Rhizopus oryzae pathogenesis

Molecular Microbiology

Volumn 77, Issue 3, 2010, Pages 587-604

  Ibrahim, Ashraf S ^a,b   Gebremariam, Teclegiorgis ^a   Lin, Lin ^a   Luo, Guanpingsheng ^a   Husseiny, Mohamed I ^a,d   Skory, Christopher D ^c   Fu, Yue ^a,b   French, Samuel W ^a,b   Edwards Jr , John E ^a,b   Spellberg, Brad ^a  

^a HARBOR UCLA MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c NATIONAL CENTER FOR AGRICULTURAL UTILIZATION RESEARCH   (United States)

^d Zagazig University   (Egypt)

Author keywords

[No Author keywords available]

Indexed keywords

IRON; IRON PERMEASE; PERMEASE; UNCLASSIFIED DRUG; CARRIER PROTEIN; FUNGAL PROTEIN; PROTEIN BINDING; VIRULENCE FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DIABETIC KETOACIDOSIS; FUNGAL VIRULENCE; GENE DISRUPTION; GENE EXPRESSION; GENETIC RECOMBINATION; HISTOPATHOLOGY; IN VITRO STUDY; IRON BINDING CAPACITY; IRON BLOOD LEVEL; MALE; MOUSE; MUCORMYCOSIS; NONHUMAN; NULL ALLELE; PASSIVE IMMUNIZATION; PATHOGENESIS; PRIORITY JOURNAL; RHIZOPUS ORYZAE; RNA INTERFERENCE; ANIMAL; BAGG ALBINO MOUSE; ENZYMOLOGY; GENETICS; HUMAN; METABOLISM; MICROBIOLOGY; PATHOGENICITY; RHIZOPUS;

ANIMALIA; MUS; RHIZOPUS ORYZAE;

ANIMALS; DIABETIC KETOACIDOSIS; FUNGAL PROTEINS; HUMANS; IRON; MALE; MEMBRANE TRANSPORT PROTEINS; MICE; MICE, INBRED BALB C; MUCORMYCOSIS; PROTEIN BINDING; RHIZOPUS; VIRULENCE FACTORS;

EID: 77954848386     PISSN: 0950382X     EISSN: 13652958     Source Type: Journal    
DOI: 10.1111/j.1365-2958.2010.07234.x     Document Type: Article

References (68)

1. Allen, C.E. Schmitt, M.P. (2009) HtaA is an iron-regulated hemin binding protein involved in the utilization of heme iron in Corynebacterium diphtheriae. J Bacteriol 191 : 2638 2648.
2. Artis, W.M., Fountain, J.A., Delcher, H.K. Jones, H.E. (1982) A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability. Diabetes 31 : 1109 1114.
3. Boelaert, J.R., Vergauwe, P.L. Vandepitte, J.M. (1987) Mucormycosis infection in dialysis patients [letter]. Ann Intern Med 107 : 782 783.
4. Boelaert, J.R., van Roost, G.F., Vergauwe, P.L., Verbanck, J.J., de Vroey, C. Segaert, M.F. (1988) The role of desferrioxamine in dialysis-associated mucormycosis: report of three cases and review of the literature. Clin Nephrol 29 : 261 266.
5. Boelaert, J.R., de Locht, M., Cutsem, J.V., Kerrels, V., Cantinieaux, B., Verdonck, A., et al. (1993) Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies. J Clin Invest 91 : 1979 1986.
6. Boelaert, J.R., Van Cutsem, J., de Locht, M., Schneider, Y.J. Crichton, R.R. (1994) Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect. Kidney Int 45 : 667 671.
7. Brand, A., MacCallum, D.M., Brown, A.J., Gow, N.A. Odds, F.C. (2004) Ectopic expression of URA3 can influence the virulence phenotypes and proteome of Candida albicans but can be overcome by targeted reintegration of URA3 at the RPS10 locus. Eukaryot Cell 3 : 900 909.
8. D'Enfert, C., Diaquin, M., Delit, A., Wuscher, N., Debeaupuis, J.P., Huerre, M. Latge, J.P. (1996) Attenuated virulence of uridine-uracil auxotrophs of Aspergillus fumigatus. Infect Immun 64 : 4401 4405.
9. Dix, D.R., Bridgham, J.T., Broderius, M.A., Byersdorfer, C.A. Eide, D.J. (1994) The FET4 gene encodes the low affinity Fe(II) transport protein of Saccharomyces cerevisiae. J Biol Chem 269 : 26092 26099.
10. 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.
11. Fu, Y., Lee, H., Collins, M., Tsai, H.F., Spellberg, B., Edwards, J.E., et al. (2004) Cloning and functional characterization of the Rhizopus oryzae high affinity iron permease (rFTR1) gene. FEMS Microbiol Lett 235 : 169 176.
12. Gleissner, B., Schilling, A., Anagnostopolous, I., Siehl, I. Thiel, E. (2004) Improved outcome of zygomycosis in patients with hematological diseases? Leuk Lymphoma 45 : 1351 1360.
13. Gravelat, F.N., Doedt, T., Chiang, L.Y., Liu, H., Filler, S.G., Patterson, T.F. Sheppard, D.C. (2008) In vivo analysis of Aspergillus fumigatus developmental gene expression determined by real-time reverse transcription-PCR. Infect Immun 76 : 3632 3639.
14. Heymann, P., Gerads, M., Schaller, M., Dromer, F., Winkelmann, G. Ernst, J.F. (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.
15. Hissen, A.H., Chow, J.M., Pinto, L.J. Moore, M.M. (2004) Survival of Aspergillus fumigatus in serum involves removal of iron from transferrin: the role of siderophores. Infect Immun 72 : 1402 1408.
16. Hissen, A.H., Wan, A.N., Warwas, M.L., Pinto, L.J. Moore, M.M. (2005) The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence. Infect Immun 73 : 5493 5503.
17. Ibrahim, A.S., Avanessian, V., Spellberg, B. Edwards, J.E., Jr. (2003a) Liposomal amphotericin B, and not amphotericin B deoxycholate, improves survival of diabetic mice infected with Rhizopus oryzae. Antimicrob Agents Chemother 47 : 3343 3344.
18. Ibrahim, A.S., Edwards, J.E., Jr. Filler, S.G. (2003b) Zygomycosis. In Clinical Mycology. Dismukes, W.E., Pappas, P.G. Sobel, J.D. (eds).
19. Ibrahim, A.S., Bowman, J.C., Avanessian, V., Brown, K., Spellberg, B., Edwards, J.E., Jr. Douglas, C.M. (2005a) Caspofungin inhibits Rhizopus oryzae 1,3-beta-D-glucan synthase, lowers burden in brain measured by quantitative PCR, and improves survival at a low but not a high dose during murine disseminated zygomycosis. Antimicrob Agents Chemother 49 : 721 727.
20. Ibrahim, A.S., Spellberg, B.J., Avenissian, V., Fu, Y., Filler, S.G. Edwards, J.E., Jr. (2005b) Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity. Infect Immun 73 : 999 1005.
21. Ibrahim, A.S., Edwards, J.E., Jr., Fu, Y. Spellberg, B. (2006) Deferiprone iron chelation as a novel therapy for experimental mucormycosis. J Antimicrob Chemother 58 : 1070 1073.
22. Ibrahim, A.S., Gebermariam, T., Fu, Y., Lin, L., Husseiny, M.I., French, S.W., et al. (2007) The iron chelator deferasirox protects mice from mucormycosis through iron starvation. J Clin Invest 117 : 2649 2657.
23. Ibrahim, A.S., Spellberg, B. Edwards, J., Jr. (2008) Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment. Curr Opin Infect Dis 21 : 620 625.
24. Jung, W.H., Sham, A., Lian, T., Singh, A., Kosman, D.J. Kronstad, J.W. (2008) Iron source preference and regulation of iron uptake in Cryptococcus neoformans. PLoS Pathog 4 : e45.
25. Kauffman, C.A. (2004) Zygomycosis: reemergence of an old pathogen. Clin Infect Dis 39 : 588 590.
26. Kirsch, D.R. Whitney, R.R. (1991) Pathogenicity of Candida albicans auxotrophic mutants in experimental infections. Infect Immun 59 : 3297 3300.
27. 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.
28. Knight, S.A., Vilaire, G., Lesuisse, E. Dancis, A. (2005) Iron acquisition from transferrin by Candida albicans depends on the reductive pathway. Infect Immun 73 : 5482 5492.
29. Kontoyiannis, D.P., Wessel, V.C., Bodey, G.P. Rolston, K.V. (2000) Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis 30 : 851 856.
30. Kwon-Chung, K.J. Bennett, J.E. (1992) Mucormycosis. In Medical Mycology.
31. Lay, J., Henry, L.K., Clifford, J., Koltin, Y., Bulawa, C.E. Becker, J.M. (1998) Altered expression of selectable marker URA3 in gene-disrupted Candida albicans strains complicates interpretation of virulence studies. Infect Immun 66 : 5301 5306.
32. 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.
33. 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.
34. Liu, M., Tanaka, W.N., Zhu, H., Xie, G., Dooley, D.M. Lei, B. (2008) Direct hemin transfer from IsdA to IsdC in the iron-regulated surface determinant (Isd) heme acquisition system of Staphylococcus aureus. J Biol Chem 283 : 6668 6676.
35. Livak, K.J. Schmittgen, T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25 : 402 408.
36. de Locht, M., Boelaert, J.R. Schneider, Y.J. (1994) Iron uptake from ferrioxamine and from ferrirhizoferrin by germinating spores of Rhizopus microsporus. Biochem Pharmacol 47 : 1843 1850.
37. Ma, L.J., Ibrahim, A.S., Skory, C., Grabherr, M.G., Burger, G., Butler, M., et al. (2009) Genomic analysis of the basal lineage fungus Rhizopus oryzae reveals a whole-genome duplication. PLoS Genet 5 : e1000549.
38. Marr, K.A., Carter, R.A., Crippa, F., Wald, A. Corey, L. (2002) Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 34 : 909 917. (Pubitemid 34229758)
39. Mertens, J.A., Skory, C.D. Ibrahim, A.S. (2006) Plasmids for expression of heterologous proteins in Rhizopus oryzae. Arch microbiol 186 : 41 50.
40. Nakayashiki, H., Hanada, S., Nguyen, B.Q., Kadotani, N., Tosa, Y. Mayama, S. (2005) RNA silencing as a tool for exploring gene function in ascomycete fungi. Fungal Genet Biol 42 : 275 283.
41. Park, Y.S., Choi, I.D., Kang, C.M., Ham, M.S., Kim, J.H., Kim, T.H., et al. (2006) Functional identification of high-affinity iron permeases from Fusarium graminearum. Fungal Genet Biol 43 : 273 282.
42. Pendrak, M.L., Chao, M.P., Yan, S.S. Roberts, D.D. (2004) Heme oxygenase in Candida albicans is regulated by hemoglobin and is necessary for metabolism of exogenous heme and hemoglobin to alpha-biliverdin. J Biol Chem 279 : 3426 3433.
43. Pfaffl, M.W. (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29 : e45.
44. Pierson, C.A., Jia, N., Mo, C., Lees, N.D., Sturm, A.M., Eckstein, J., et al. (2004) Isolation, characterization, and regulation of the Candida albicans ERG27 gene encoding the sterol 3-keto reductase. Med Mycol 42 : 461 473.
45. Ramanan, N. Wang, Y. (2000) A high-affinity iron permease essential for Candida albicans virulence. Science 288 : 1062 1064.
46. Reed, C., Bryant, R., Ibrahim, A.S., Edwards, J., Jr., Filler, S.G., Goldberg, R. Spellberg, B. (2008) Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis 47 : 364 371. (Pubitemid 352009357)
47. Ribes, J.A., Vanover-Sams, C.L. Baker, D.J. (2000) Zygomycetes in human disease. Clin Microbiol Rev 13 : 236 301.
48. Roden, M.M., Zaoutis, T.E., Buchanan, W.L., Knudsen, T.A., Sarkisova, T.A., Schaufele, R.L., et al. (2005) Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 41 : 634 653.
49. Santos, R., Buisson, N., Knight, S., Dancis, A., Camadro, J.M. Lesuisse, E. (2003) Haemin uptake and use as an iron source by Candida albicans: role of CaHMX1-encoded haem oxygenase. Microbiology 149 : 579 588.
50. Sanyal, K. Carbon, J. (2002) The CENP-A homolog CaCse4p in the pathogenic yeast Candida albicans is a centromere protein essential for chromosome transmission. Proc Natl Acad Sci USA 99 : 12969 12974.
51. Schrettl, M., Bignell, E., Kragl, C., Joechl, C., Rogers, T., Arst, H.N., et al. (2004) Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence. J Exp Med 200 : 1213 1219.
52. Siwek, G.T., Dodgson, K.J., de Magalhaes-Silverman, M., Bartelt, L.A., Kilborn, S.B., Hoth, P.L., et al. (2004) Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin Infect Dis 39 : 584 587.
53. Skory, C.D. (2002) Homologous recombination and double-strand break repair in the transformation of Rhizopus oryzae. Mol Genet Genomics 268 : 397 406.
54. Skory, C.D. (2003) Induction of Rhizopus oryzae pyruvate decarboxylase genes. Curr Microbiol 47 : 59 64.
55. Skory, C.D. (2005) Inhibition of non-homologous end joining and integration of DNA upon transformation of Rhizopus oryzae. Mol Genet Genomics 274 : 373 383.
56. Skory, C.D. Ibrahim, A.S. (2007) Native and modified lactate dehydrogenase expression in a fumaric acid producing isolate Rhizopus oryzae 99-880. Curr Genet 52 : 23 33.
57. Spellberg, B., Edwards, J. Jr. Ibrahim, A. (2005) Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev 18 : 556 569.
58. 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.
59. Stojiljkovic, I. Hantke, K. (1994) Transport of haemin across the cytoplasmic membrane through a haemin-specific periplasmic binding-protein- dependent transport system in Yersinia enterocolitica. Mol Microbiol 13 : 719 732.
60. Sugar, A.M. (2005) Agents of mucormycosis and related species. In Principles and Practice of Infectious Diseases. Mandell, G.L., Bennett, J.E. Dolin, R. (eds).
61. Sundstrom, P., Cutler, J.E. Staab, J.F. (2002) Reevaluation of the role of HWP1 in systemic candidiasis by use of Candida albicans strains with selectable marker URA3 targeted to the ENO1 locus. Infect Immun 70 : 3281 3283.
62. Thieken, A. Winkelmann, G. (1992) Rhizoferrin: a complexone type siderophore of the Mucorales and entomophthorales (Zygomycetes). FEMS Microbiol Lett 73 : 37 41.
63. Varma, A., Edman, J.C. Kwon-Chung, K.J. (1992) Molecular and genetic analysis of URA5 transformants of Cryptococcus neoformans. Infect Immun 60 : 1101 1108.
64. Waldorf, A.R., Ruderman, N. Diamond, R.D. (1984) Specific susceptibility to mucormycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus. J Clin Invest 74 : 150 160.
65. Weissman, Z. Kornitzer, D. (2004) A family of Candida cell surface haem-binding proteins involved in haemin and haemoglobin-iron utilization. Mol Microbiol 53 : 1209 1220.
66. Weissman, Z., Shemer, R., Conibear, E. Kornitzer, D. (2008) An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans. Mol Microbiol 69 : 201 217.
67. Wesley, S.V., Helliwell, C.A., Smith, N.A., Wang, M.B., Rouse, D.T., Liu, Q., et al. (2001) Construct design for efficient, effective and high-throughput gene silencing in plants. Plant J 27 : 581 590.
68. Zhu, H., Xie, G., Liu, M., Olson, J.S., Fabian, M., Dooley, D.M. Lei, B. (2008) Pathway for heme uptake from human methemoglobin by the iron-regulated surface determinants system of Staphylococcus aureus. J Biol Chem 283 : 18450 18460.