Hemizygosity Enables a Mutational Transition Governing Fungal Virulence and Commensalism

Cell Host Microbe. 2019 Mar 13;25(3):418-431.e6. doi: 10.1016/j.chom.2019.01.005. Epub 2019 Feb 26.


Candida albicans is a commensal fungus of human gastrointestinal and reproductive tracts, but also causes life-threatening systemic infections. The balance between colonization and pathogenesis is associated with phenotypic plasticity, with alternative cell states producing different outcomes in a mammalian host. Here, we reveal that gene dosage of a master transcription factor regulates cell differentiation in diploid C. albicans cells, as EFG1 hemizygous cells undergo a phenotypic transition inaccessible to "wild-type" cells with two functional EFG1 alleles. Notably, clinical isolates are often EFG1 hemizygous and thus licensed to undergo this transition. Phenotypic change corresponds to high-frequency loss of the functional EFG1 allele via de novo mutation or gene conversion events. This phenomenon also occurs during passaging in the gastrointestinal tract with the resulting cell type being hypercompetitive for commensal and systemic infections. A "two-hit" genetic model therefore underlies a key phenotypic transition in C. albicans that enables adaptation to host niches.

Keywords: Candida albicans; gastrointestinal tract; pathogenesis; phase variation; phenotypic switch; population genetics; transcription factor.

Publication types

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

MeSH terms

  • Candida albicans / genetics*
  • Candida albicans / growth & development*
  • Candida albicans / pathogenicity
  • Candidiasis / microbiology*
  • DNA-Binding Proteins / genetics
  • Fungal Proteins / genetics
  • Gastrointestinal Tract / microbiology*
  • Gene Dosage
  • Gene Expression Regulation, Fungal*
  • Humans
  • Mutation*
  • Symbiosis*
  • Transcription Factors / genetics
  • Virulence


  • DNA-Binding Proteins
  • EFG1 protein, Candida albicans
  • Fungal Proteins
  • Transcription Factors