Candida Albicans Transcription Factor Rim101 Mediates Pathogenic Interactions Through Cell Wall Functions

Cell Microbiol. 2008 Nov;10(11):2180-96. doi: 10.1111/j.1462-5822.2008.01198.x. Epub 2008 Jul 4.

Abstract

pH-responsive transcription factors of the Rim101/PacC family govern virulence in many fungal pathogens. These family members control expression of target genes with diverse functions in growth, morphology and environmental adaptation, so the mechanistic relationship between Rim101/PacC and infection is unclear. We have focused on Rim101 from Candida albicans, which we find to be required for virulence in an oropharyngeal candidiasis model. Rim101 affects the yeast-hypha morphological transition, a major virulence requirement in disseminated infection models. However, virulence in the oropharyngeal candidiasis model is independent of the yeast-hypha transition because it is unaffected by an nrg1 mutation, which prevents formation of yeast cells. Here we have identified Rim101 target genes in an nrg1Delta/Delta mutant background and surveyed function using an overexpression-rescue approach. Increased expression of Rim101 target genes ALS3, CHT2, PGA7/RBT6, SKN1 or ZRT1 can partially restore pathogenic interaction of a rim101Delta/Delta mutant with oral epithelial cells. Four of these five genes govern cell wall structure. Our results indicate that Rim101-dependent cell wall alteration contributes to C. albicans pathogenic interactions with oral epithelial cells, independently of cell morphology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Candida albicans / cytology*
  • Candida albicans / genetics
  • Candida albicans / metabolism
  • Candida albicans / pathogenicity*
  • Candidiasis / metabolism
  • Cell Line
  • Cell Shape
  • Cell Wall / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epithelial Cells / cytology
  • Epithelial Cells / microbiology
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • Genetic Complementation Test
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microarray Analysis
  • Mouth Mucosa / cytology
  • Mouth Mucosa / microbiology
  • Mouth Mucosa / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Fungal Proteins
  • RIM101 protein, Candida albicans
  • Transcription Factors