Deletion of the high-affinity cAMP phosphodiesterase encoded by PDE2 affects stress responses and virulence in Candida albicans.
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.
Wilson
Duncan
D
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Tutulan-Cunita
Andreea
A
Jung
WonHee
W
Hauser
Nicole C
NC
Hernandez
Rosa
R
Williamson
Tom
T
Piekarska
Katarzyna
K
Rupp
Steffen
S
Young
Tim
T
Stateva
Lubomira
L
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005800:Genes, Fungal; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D017510:Protein Folding; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology; D013045:Species Specificity; D014158:Transcription, Genetic / Q000187:drug effects; D014774:Virulence / Q000187:drug effects
D005656:Fungal Proteins; D012333:RNA, Messenger; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; C517275:PDE2A protein, human; C517277:Pde2a protein, mouse