Deletion of the high-affinity cAMP phosphodiesterase encoded by PDE2 affects stress responses and virulence in Candida albicans

Duncan Wilson, Andreea Tutulan-Cunita, WonHee Jung, Nicole C Hauser, Rosa Hernandez, Tom Williamson, Katarzyna Piekarska, Steffen Rupp, Tim Young, Lubomira Stateva

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Previously, we have shown that PDE2 is required for hyphal development and cell wall integrity in Candida albicans. In the present study, we have investigated the effects of its deletion by genome-wide transcriptome profiling. Changes in expression levels of genes involved in metabolism, transcription, protein and nucleic acids synthesis, as well as stress responses, cell wall and membrane biogenesis, adherence and virulence have been observed. By comparing these changes with previously reported transcriptome profiles of pde2Delta mutants of Saccharomyces cerevisiae, as well as cdc35Delta, ras1Delta and efg1Delta mutants of C. albicans, conserved and species-specific cAMP-regulated genes have been identified. The genes whose transcription is altered upon deletion of PDE2 in C. albicans has also allowed us to predict that the pde2Delta mutant would have a defective ability to adhere to, and invade host cells, and an impaired virulence as well as response to different stresses. Using appropriate assays, we have tested these predictions and compared the roles of the high- and low-affinity cAMP phosphodiesterases, Pde2p and Pde1p in stress, adhesion and virulence. We suggest that phosphodiesterases, and in particular the high-affinity cAMP phosphodiesterase encoded by PDE2, have real potential as targets for antifungal chemotherapy.
Original languageEnglish
Pages (from-to)841-856
Number of pages16
JournalMolecular Microbiology
Volume65
Issue number4
Early online date3 Jun 2007
DOIs
Publication statusPublished - Aug 2007

Keywords

  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Animals
  • Candida albicans
  • Cyclic AMP
  • Cyclic Nucleotide Phosphodiesterases, Type 1
  • Cyclic Nucleotide Phosphodiesterases, Type 2
  • Fungal Proteins
  • Gene Deletion
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Humans
  • Mice
  • Mutation
  • Phosphoric Diester Hydrolases
  • Protein Folding
  • Protein Processing, Post-Translational
  • Protein Transport
  • RNA, Messenger
  • Saccharomyces cerevisiae
  • Species Specificity
  • Transcription, Genetic
  • Virulence

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