Abstract

Iron present in loosely bound or unchelated forms within cells can act catalytically to produce DNA damaging and lipid peroxidizing oxygen radicals. Oxidative damage of cells is now thought to be causally related to many widespread human diseases including arthritis, atherosclerosis, cancer and cellular aging. An understanding of the mechanisms by which organisms regulate uptake of iron and store intracellular iron is central to an understanding of the etiology of these diseases as well as infectious disease. The ability of microbial pathogens to acquire iron from the host is an important component of virulence. While much progress has been made in determining the molecular details of iron uptake in procaryotes, a comparable description in eucaryotes is lacking. This proposal addresses the molecular analysis of a genetically accessible, eucaryotic iron assimilation system. The siderophore-mediated high affinity iron transport system of Ustilago maydis, the cause of corn smut disease, will be studied. The molecular mechanism of biosynthesis of the siderophore ferrichrome will be delineated by molecular and genetic analysis of the genes controlling ferrichrome biogenesis and by isolating and characterizing the products specified by these genes. The phytopathogenicity and survival of U. maydis mutants unable to produce siderophores will also be investigated. These studies will provide the first molecular description of a siderophore biosynthetic pathway in a eucaryotic organism and provide information on the biologic role of siderophores in the life cycle of this fungus.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033716-06
Application #
3283663
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1986-09-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Yuan, W M; Gentil, G D; Budde, A D et al. (2001) Characterization of the Ustilago maydis sid2 gene, encoding a multidomain peptide synthetase in the ferrichrome biosynthetic gene cluster. J Bacteriol 183:4040-51
Leong, S A; Winkelmann, G (1998) Molecular biology of iron transport in fungi. Met Ions Biol Syst 35:147-86
An, Z; Zhao, Q; McEvoy, J et al. (1997) The second finger of Urbs1 is required for iron-mediated repression of sid1 in Ustilago maydis. Proc Natl Acad Sci U S A 94:5882-7
An, Z; Mei, B; Yuan, W M et al. (1997) The distal GATA sequences of the sid1 promoter of Ustilago maydis mediate iron repression of siderophore production and interact directly with Urbs1, a GATA family transcription factor. EMBO J 16:1742-50
An, Z; Farman, M L; Budde, A et al. (1996) New cosmid vectors for library construction, chromosome walking and restriction mapping in filamentous fungi. Gene 176:93-6
Mei, B; Budde, A D; Leong, S A (1993) sid1, a gene initiating siderophore biosynthesis in Ustilago maydis: molecular characterization, regulation by iron, and role in phytopathogenicity. Proc Natl Acad Sci U S A 90:903-7
Voisard, C; Wang, J; McEvoy, J L et al. (1993) urbs1, a gene regulating siderophore biosynthesis in Ustilago maydis, encodes a protein similar to the erythroid transcription factor GATA-1. Mol Cell Biol 13:7091-100
Saville, B J; Leong, S A (1992) The molecular biology of pathogenesis in Ustilago maydis. Genet Eng (N Y) 14:139-62
Froeliger, E H; Leong, S A (1991) The a mating-type alleles of Ustilago maydis are idiomorphs. Gene 100:113-22
Smith, T L; Leong, S A (1990) Isolation and characterization of a Ustilago maydis glyceraldehyde-3-phosphate dehydrogenase-encoding gene. Gene 93:111-7

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