Iron acquisition: A novel perspective on mucormycosis pathogenesis and treatment

Current Opinion in Infectious Diseases

Volumn 21, Issue 6, 2008, Pages 620-625

  Ibrahim, Ashraf S ^a,b   Spellberg, Brad ^a,b   Edwards Jr , John ^a,b  

^a HARBOR UCLA MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Deferasirox; Deferiprone; Iron chelation; Mucormycosis; Rhizopus

Indexed keywords

AMPHOTERICIN B; CASPOFUNGIN; DEFERASIROX; DEFERIPRONE; DEFEROXAMINE; HEMIN; IRON; OXIDOREDUCTASE; PERMEASE; POLYENE; SIDEROPHORE;

DRUG ACTIVITY; DRUG MECHANISM; FUNGUS; HUMAN; IN VITRO STUDY; IRON CHELATION; IRON METABOLISM; IRON TRANSPORT; KIDNEY FAILURE; MUCORMYCOSIS; NEPHROTOXICITY; NONHUMAN; OUTCOME ASSESSMENT; PATHOGENESIS; REVIEW; RISK ASSESSMENT; RISK FACTOR; SALVAGE THERAPY; ZYGOMYCETES;

ANIMALS; BENZOIC ACIDS; CHELATING AGENTS; DEFEROXAMINE; HUMANS; IRON; MICROBIAL VIABILITY; MUCORALES; MUCORMYCOSIS; PYRIDONES; TRIAZOLES;

EID: 57049181320     PISSN: 09517375     EISSN: None     Source Type: Journal    
DOI: 10.1097/QCO.0b013e3283165fd1     Document Type: Review

References (42)

1. Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev 2000; 13:236-301.
2. Spellberg B, Edwards J Jr, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev 2005; 18:556-569.
3. Gleissner B, Schilling A, Anagnostopolous I, et al. Improved outcome of zygomycosis in patients with hematological diseases? Leuk Lymphoma 2004; 45:1351-1360.
4. Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KV. Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis 2000; 30:851-856.
5. Marr KA, Carter RA, Crippa F, et al. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002; 34:909-917.
6. Edwards J Jr. Zygomycosis. In: Hoeprich P, Jordan M, editors. Infectious disease, 4th ed. J.B. Lippincott Co.; 1989. pp. 1192-1199.
7. Ibrahim AS, Edwards JEJ, Filler SG. Zygomycosis. In: Dismukes WE, Pappas PG, Sobel JD, editors. Clinical mycology. Oxford University Press; 2003 pp. 241-251.
8. Kwon-Chung KJ, Bennett JE, editors. Mucormycosis. In: Medical mycology. Philadelphia: Lea & Febiger; 1992. pp. 524-559.
9. Sugar AM. Agent of mucormycosis and related species. In: Mandell G, Bennett J, Dolin R, editors. Principles and practices of infectious diseases, 4th ed. Churchill Livingstone; 1995. pp. 2311-2321.
10. Husain S, Alexander BD, Munoz P, et al. Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi. Clin Infect Dis 2003; 37:221-229.
11. Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis 2008; 47:364-371. This retrospective study describes the successful use of combination of polyene and caspofungin in treating patients with rhino-orbital-cerebral mucormycosis; therefore, possibly identifying a more efficacious treatment of mucormycosis.
12. Howard DH. Acquisition, transport, and storage of iron by pathogenic fungi. Clin Microbiol Rev 1999; 12:394-404.
13. Artis WM, Fountain JA, Delcher HK, Jones HE. A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability. Diabetes 1982; 31:1109-1114.
14. Boelaert JR, de Locht M, Van Cutsem J, et al. Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies. J Clin Invest 1993; 91:1979-1986.
15. Boelaert JR, Van Cutsem J, de Locht M, et al. Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect. Kidney Int 1994; 45:667-671.
16. de Locht M, Boelaert JR, Schneider YJ. Iron uptake from ferrioxamine and from ferrirhizoferrin by germinating spores of Rhizopus microsporus. Biochem Pharmacol 1994; 47:1843-1850.
17. Eide D, Davis-Kaplan S, Jordan I, et al. Regulation of iron uptake in Saccharomyces cerevisiae. The ferrireductase and Fe(II) transporter are regulated independently. J Biol Chem 1992; 267:20774-20781.
18. Lesuisse E, Labbe P. Reductive iron assimilation in Saccharomyces cerevisiae. In: Winkelmann G, Winge DR, editors. Metal ions in fungi. Vol. 11. New York: Marcel Dekker, Inc.; 1994. pp. 149-178.
19. Matzanke BF. Iron storage in fungi. In: Winkelmann G, Winge DR, editors. Metal ions in fungi. Vol. 11. New York: Marcel Dekker, Inc.; 1994. pp. 179-214.
20. Carrano CJ, Bohnke R, Matzanke BF. Fungal ferritins: the ferritin from mycelia of Absidia spinosa is a bacterioferritin. FEBS Lett 1996; 390:261-264.
21. Dix DR, Bridgham JT, Broderius MA, et al. The FET4 gene encodes the low affinity Fe(II) transport protein of Saccharomyces cerevisiae. J Biol Chem 1994; 269:26092-26099.
22. Eck R, Hundt S, Hartl A, et al. A multicopper oxidase gene from Candida albicans: cloning, characterization and disruption. Microbiology 1999; 145(Pt 9):2415-2422.
23. Knight SA, Lesuisse E, Stearman R, et al. Reductive iron uptake by Candida albicans: role of copper, iron and the TUP1 regulator. Microbiology 2002; 148:29-40.
24. Ramanan N, Wang Y. A high-affinity iron permease essential for Candida albicans virulence. Science 2000; 288:1062-1064.
25. Lesuisse E, Knight SA, Camadro JM, Dancis A. Siderophore uptake by Candida albicans: effect of serum treatment and comparison with Saccharomyces cerevisiae. Yeast 2002; 19:329-340.
26. Lesuisse E, Simon-Casteras M, Labbe P. Siderophore-mediated iron uptake in Saccharomyces cerevisiae: the SIT1 gene encodes a ferrioxamine B permease that belongs to the major facilitator superfamily. Microbiology 1998; 144 (Pt 12):3455-3462.
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; 70:5246-5255.
28. 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; 149:579-588.
29. Stearman R, Yuan DS, Yamaguchi-Iwai Y, et al. A permease-oxidase complex involved in high-affinity iron uptake in yeast. Science 1996; 271:1552-1557.
30. Casas C, Aldea M, Espinet C, et al. The AFT1 transcriptional factor is differentially required for expression of high-affinity iron uptake genes in Saccharomyces cerevisiae. Yeast 1997; 13:621-637.
31. Fu Y, Lee H, Collins M, et al. Cloning and functional characterization of the Rhizopus oryzae high affinity iron permease (rFTR1) gene. FEMS Microbiol Lett 2004; 235:169-176.
32. Lin L, Spellberg B, Fu Y, et al. High affinity iron permease is required for virulence of Rhizopus oryzae [abstract # B-1444]. In: 47th Interscience Conference On Antimicrobial Agents And Chemotherapy; 17-20 September 2007; Chicago, Illinois: American Society for Microbiology; 2007.
33. Guerinot ML. Microbial iron transport. Annu Rev Microbiol 1994; 48:743-772.
34. Carrano CJ, Raymond KN. Coordination chemistry of microbial iron transport compounds: rhodotorulic acid and iron uptake in Rhodotorula pilimanae. J Bacteriol 1978; 136:69-74.
35. Winkelmann G. Kinetics, energetics, and mechanisms of siderophore iron transport in fungi. In: Barton LL. Ed. Iron chelation in plants and soil micro-organisms. Academic Press, Inc.; 1993:219-239.
36. Thieken A, Winkelmann G. Rhizoferrin: a complexone type siderophore of the Mucorales and entomophthorales (Zygomycetes). FEMS Microbiol Lett 1992; 73:37-41.
37. Reissbrodt R, Kingsley R, Rabsch W, et al. Iron-regulated excretion of alpha-keto acids by Salmonella typhimurium. J Bacteriol 1997; 179:4538-4544.
38. Worsham PL, Goldman WE. Quantitative plating of Histoplasma capsulatum without addition of conditioned medium or siderophores. J Med Vet Mycol 1988; 26:137-143.
39. Ibrahim AS, Edwards JE Jr, Fu Y, Spellberg B. Deferiprone iron chelation as a novel therapy for experimental mucormycosis. J Antimicrob Chemother 2006; 58:1070-1073.
40. Ibrahim AS, Gebermariam T, Fu Y, et al. The iron chelator deferasirox protects mice from mucormycosis through iron starvation. J Clin Invest 2007; 117:2649-2657. This study described that the iron chelator, deferasirox (a US FDA-approved drug), causes iron starvation and is cidal against Zygomycetes. Further, it describes the use of a novel treatment for experimental mucormycosis. The use of the iron chelator, deferasirox, was equally effective to liposomal amphotericin B in treating mucormycosis. More importantly, the use of a combination therapy of deferasirox and liposomal amphotericin B was more efficacious in treating mucormycosis than either drug alone.
41. Chamilos G, Lewis RE, Hu J, et al. Drosophila melanogaster as a model host to dissect the immunopathogenesis of zygomycosis. Proc Natl Acad Sci U S A 2008; 105:9367-9372.
42. Reed C, Ibrahim A, Edwards JE Jr, et al. Deferasirox, an iron-chelating agent, as salvage therapy for rhinocerebral mucormycosis. Antimicrob Agents Chemother 2006; 50:3968-3969.