title: Regulatory networks affected by iron availability in Candida albicans.
abstract: Iron, an essential element for almost every organism, serves as a regulatory signal for the expression of virulence determinants in many prokaryotic and eukaryotic pathogens. Using a custom Affymetrix GeneChip representing the entire Candida albicans genome, we examined the changes in genome-wide gene expression in this opportunistic pathogen as a function of alterations in environmental concentrations of iron. A total of 526 open reading frame (ORF) transcripts are more highly expressed when the levels of available iron are low, while 626 ORF transcripts are more highly expressed in high-iron conditions. The transcripts dominantly affected by iron concentration range from those associated with cell-surface properties to others which affect mitochondrial function, iron transport and virulence-related secreted hydrolases. Moreover gene expression as assayed in DNA microarrays confirms and extends reports of alterations in cell-surface antigens and drug sensitivity correlated with iron availability. To understand how these genes and pathways might be regulated, we isolated a gene designated SFU1 that encodes a homologue of the Ustilago maydis URBS1, a transcriptional repressor of siderophore uptake/biosynthesis. Comparisons between wild-type and SFU1-null mutant strains revealed 139 potential target genes of Sfu1p; many of which are iron-responsive. Together, these results not only expand our understanding of global iron regulation in C. albicans, but also provide insights into the potential role of iron availability in C. albicans virulence.
authors.affiliation: Department of Stomatology, University of California, San Francisco, CA 94143, USA.
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Lan
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rodarte
authors.forename: Luis A
authors.initials: LA
authors.lastname: Murillo
authors.forename: Ted
authors.initials: T
authors.lastname: Jones
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Davis
authors.forename: Jan
authors.initials: J
authors.lastname: Dungan
authors.forename: George
authors.initials: G
authors.lastname: Newport
authors.forename: Nina
authors.initials: N
authors.lastname: Agabian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D007501:Iron / Q000378:metabolism*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D033902:Periplasmic Binding Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D005656:Fungal Proteins; D033902:Periplasmic Binding Proteins; C062885:sfu proteins, Serratia marcescens; D007501:Iron