An Iron Homeostasis Regulatory Circuit With Reciprocal Roles in Candida Albicans Commensalism and Pathogenesis

Cell Host Microbe. 2011 Aug 18;10(2):118-35. doi: 10.1016/j.chom.2011.07.005.

Abstract

The mammalian gastrointestinal tract and bloodstream are highly disparate biological niches that differ in concentrations of nutrients such as iron. However, some commensal-pathogenic microorganisms, such as the yeast Candida albicans, thrive in both environments. We report the evolution of a transcription circuit in C. albicans that controls iron uptake and determines its fitness in both niches. Our analysis of DNA-binding proteins that regulate iron uptake by this organism suggests the evolutionary intercalation of a transcriptional activator called Sef1 between two broadly conserved iron-responsive transcriptional repressors, Sfu1 and Hap43. Sef1 activates iron-uptake genes and promotes virulence in a mouse model of bloodstream infection, whereas Sfu1 represses iron-uptake genes and is dispensable for virulence but promotes gastrointestinal commensalism. Thus, C. albicans can alternate between genetic programs conferring resistance to iron depletion in the bloodstream versus iron toxicity in the gut, and this may represent a fundamental attribute of gastrointestinal commensal-pathogens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Candida albicans / genetics
  • Candida albicans / growth & development
  • Candida albicans / pathogenicity*
  • Chromatin Immunoprecipitation / methods
  • Female
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • Homeostasis*
  • Humans
  • Iron / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Phylogeny
  • Plasma / metabolism
  • Plasma / microbiology
  • Promoter Regions, Genetic
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Symbiosis*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transcriptional Activation
  • Virulence

Substances

  • Fungal Proteins
  • Repressor Proteins
  • Transcription Factors
  • Iron

Associated data

  • GEO/GSE30593