A unique iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis [Expression Array]

The mammalian gastrointestinal tract and the bloodstream are highly disparate biological niches, and yet certain commensal-pathogenic microorganisms are able to thrive in both environments. Here, we report the evolution of a unique transcription circuit in the yeast, Candida albicans, which determines its fitness in both host niches. Our comprehensive analysis of the DNA-binding proteins that regulate iron uptake by this organism suggests the evolutionary intercalation of a transcriptional activator called Sef1 between two broadly conserved transcriptional repressors, Sfu1 and Hap43. The Sef1 activator of iron uptake genes promotes virulence in a mouse model of bloodstream infection, whereas the Sfu1 repressor is dispensable for virulence but promotes gastrointestinal commensalism. We propose that the ability to alternate between genetic programs conferring resistance to iron depletion in the bloodstream versus iron toxicity in the gut may be a fundamental attribute of gastrointestinal commensal-pathogens. The Wild type strain (SN250) was grown in either YEPD or YEPD supplemented with iron chelator bathophenanthroline disulfonate (BPS); The sfu1Δ (SN515) mutant was grown in YEPD medium; The sef1Δ(SN330) or hap43Δ (SN694) mutant was grown YEPD supplemented with iron chelator bathophenanthroline disulfonate (BPS). 5-6 biological replicates were performed per strain per condition. RNA was prepared from these strains and samples were hybridized on custom Agilent C. albicans ORF arrays (15,000 spots/array, 70-mer probes).