Regulation of the hypoxic response in Candida albicans

Eukaryot Cell. 2010 Nov;9(11):1734-46. doi: 10.1128/EC.00159-10. Epub 2010 Sep 24.

Abstract

The regulation of the response of Candida albicans to hypoxic (low-oxygen) conditions is poorly understood. We used microarray and other transcriptional analyses to investigate the role of the Upc2 and Bcr1 transcription factors in controlling expression of genes involved in cell wall metabolism, ergosterol synthesis, and glycolysis during adaptation to hypoxia. Hypoxic induction of the ergosterol pathway is mimicked by treatment with sterol-lowering drugs (ketoconazole) and requires UPC2. Expression of three members of the family CFEM (common in several fungal extracellular membranes) of cell wall genes (RBT5, PGA7, and PGA10) is also induced by hypoxia and ketoconazole and requires both UPC2 and BCR1. Expression of glycolytic genes is induced by hypoxia but not by treatment with sterol-lowering drugs, whereas expression of respiratory pathway genes is repressed. However, Upc2 does not play a major role in regulating expression of genes required for central carbon metabolism. Our results indicate that regulation of gene expression in response to hypoxia in C. albicans is complex and is signaled both via lowered sterol levels and other unstudied mechanisms. We also show that induction of filamentation under hypoxic conditions requires the Ras1- and Cdc35-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / drug effects
  • Candida albicans / genetics
  • Candida albicans / metabolism*
  • Cell Wall / metabolism
  • Ergosterol / biosynthesis
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal / drug effects
  • Genes, Fungal
  • Glycolysis
  • Ketoconazole / pharmacology
  • Multigene Family
  • Oligonucleotide Array Sequence Analysis
  • Oxygen / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Fungal Proteins
  • Transcription Factors
  • Ketoconazole
  • Oxygen
  • Ergosterol

Associated data

  • GEO/GSE24076