The protein kinase Tor1 regulates adhesin gene expression in Candida albicans

PLoS Pathog. 2009 Feb;5(2):e1000294. doi: 10.1371/journal.ppat.1000294. Epub 2009 Feb 6.

Abstract

Eukaryotic cell growth is coordinated in response to nutrient availability, growth factors, and environmental stimuli, enabling cell-cell interactions that promote survival. The rapamycin-sensitive Tor1 protein kinase, which is conserved from yeasts to humans, participates in a signaling pathway central to cellular nutrient responses. To gain insight into Tor-mediated processes in human fungal pathogens, we have characterized Tor signaling in Candida albicans. Global transcriptional profiling revealed evolutionarily conserved roles for Tor1 in regulating the expression of genes involved in nitrogen starvation responses and ribosome biogenesis. Interestingly, we found that in C. albicans Tor1 plays a novel role in regulating the expression of several cell wall and hyphal specific genes, including adhesins and their transcriptional repressors Nrg1 and Tup1. In accord with this transcriptional profile, rapamycin induced extensive cellular aggregation in an adhesin-dependent fashion. Moreover, adhesin gene induction and cellular aggregation of rapamycin-treated cells were strongly dependent on the transactivators Bcr1 and Efg1. These findings support models in which Tor1 negatively controls cellular adhesion by governing the activities of Bcr1 and Efg1. Taken together, these results provide evidence that Tor1-mediated cellular adhesion might be broadly conserved among eukaryotic organisms.

Publication types

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

MeSH terms

  • Candida albicans / genetics*
  • Candida albicans / growth & development
  • Candida albicans / metabolism*
  • Cell Adhesion
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Cell Aggregation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal* / drug effects
  • Hyphae / growth & development
  • Hyphae / metabolism
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Sirolimus / pharmacology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • ALA1 protein, Candida albicans
  • ALS1 protein, Candida albicans
  • ALS3 protein, Candida albicans
  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • Fungal Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Transcription Factors
  • Phosphatidylinositol 3-Kinases
  • Sirolimus