BioProject

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. More...

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. Overall design: ChIP analyses to profile genome-wide of distribution of Sef1, Sfu1 and Hap43 in response to various iron availability. 12 independent ChIP experiments were performed on 6 biological replicates of the untagged control and 2 biological replicates each of Sef1-Myc, Sfu1-Myc, and Hap43-Myc. Less...