Farnesol and dodecanol effects on the Candida albicans Ras1-cAMP signalling pathway and the regulation of morphogenesis.
Candida albicans hypha formation which has been stimulated via the Ras1-cAMP-Efg1 signalling cascade is inhibited by farnesol, a C. albicans autoregulatory factor, and small molecules such as dodecanol. In cultures containing farnesol or dodecanol, hypha formation was restored upon addition of dibutyryl-cAMP. The CAI4-Ras1(G13V) strain, which carries a dominant-active variant of Ras1 and forms hyphae in the absence of inducing stimuli, grew as yeast in medium with farnesol or dodecanol; the heat shock sensitivity of the CAI4-Ras1(G13V) strain was also suppressed by these compounds. Neither Pde1 nor Pde2 was necessary for the repression of hyphal growth by farnesol or dodecanol. Two transcripts, CTA1 and HSP12, which are at higher levels upon mutation of Ras1 or Cdc35, were increased in abundance in cells grown with farnesol or dodecanol. Microscopic analysis of strains carrying CTA1 and HWP1 promoter fusions grown with intermediate concentrations of farnesol or dodecanol indicated a link between cells with the increased expression of cAMP-repressed genes and cells repressed for hypha formation. Because several cAMP-controlled outputs are affected by farnesol and dodecanol, our findings suggest that these compounds impact activity of the Ras1-Cdc35 pathway, thus leading to an alteration of C. albicans morphology.
Davis-Hanna
Amber
A
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA.
Piispanen
Amy E
AE
Stateva
Lubomira I
LI
Hogan
Deborah A
DA
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000378:metabolism; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D007851:Dodecanol / Q000494:pharmacology*; D005204:Farnesol / Q000494:pharmacology*; D005656:Fungal Proteins / Q000187:drug effects* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D006360:Heat-Shock Proteins; D006358:Hot Temperature; D025301:Hyphae / Q000187:drug effects / Q000254:growth & development; D012331:RNA, Fungal / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism
D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D012331:RNA, Fungal; D014157:Transcription Factors; D007851:Dodecanol; D005204:Farnesol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D000262:Adenylyl Cyclases