Regulatory networks affected by iron availability in Candida albicans.
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.
Lan
Chung-Yu
CY
Department of Stomatology, University of California, San Francisco, CA 94143, USA.
Rodarte
Gabriel
G
Murillo
Luis A
LA
Jones
Ted
T
Davis
Ronald W
RW
Dungan
Jan
J
Newport
George
G
Agabian
Nina
N
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
D005656:Fungal Proteins; D033902:Periplasmic Binding Proteins; C062885:sfu proteins, Serratia marcescens; D007501:Iron