Ssn6, an Important Factor of Morphological Conversion and Virulence in Candida Albicans

Mol Microbiol. 2003 Feb;47(4):1029-43. doi: 10.1046/j.1365-2958.2003.03353.x.


Candida albicans, the major fungal pathogen in humans, undergoes morphological conversion from yeasts to filamentous growth forms depending upon various environmental conditions. Here, we have identified a C. albicans gene, namely SSN6, encoding a putative global transcriptional co-repressor that is highly homologous to the Saccharomyces cerevisiae Ssn6. The isolated C. albicans SSN6 complemented the pleiotropic phenotypes of S. cerevisiae ssn6 mutation, and its expression levels declined significantly in response to a strong true hyphal inducer, serum. The mutant lacking C. albicans Ssn6 displayed a stubby pseudohyphal growth pattern, derepressed filament-specific genes in response to elevated temperature 37 degrees C and failed to develop true hyphae, extensive filamentation and virulence. Such morphological defects of ssn6/ssn6 mutant were not rescued by overexpression of Tup1, Cph1 or Efg1. Moreover, epistatic analysis showed that, as far as cell morphology was concerned, Ssn6 was epistatic to Tup1 at the higher temperature but that, at the lower temperature, the ssn6/ssn6 tup1/tup1 double mutant grew in a stubby form of pseudohyphae distinct from the phenotypes of either single mutant. Furthermore, overexpression of SSN6 in C. albicans led to enhanced filamentous growth and attenuated virulence. These findings suggest that Ssn6 may function as an activator as well as a repressor of filamentous growth and be a target for candidacidal drugs, as its excess or deficiency resulted in impaired virulence.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Candida albicans / genetics
  • Candida albicans / growth & development*
  • Candida albicans / pathogenicity*
  • Candida albicans / physiology
  • DNA, Fungal / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Female
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology*
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Genetic Complementation Test
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Phenotype
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / pathogenicity
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Virulence


  • CPH1 protein, Candida albicans
  • CYC8 protein, S cerevisiae
  • DNA, Fungal
  • DNA-Binding Proteins
  • EFG1 protein, Candida albicans
  • Fungal Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • TUP1 protein, S cerevisiae
  • Transcription Factors