Deletion of PDE2, the gene encoding the high-affinity cAMP phosphodiesterase, results in changes of the cell wall and membrane in Candida albicans.
A role for the cAMP-dependent pathway in regulation of the cell wall in the model yeast Saccharomyces cerevisiae has recently been demonstrated. In this study we report the results of a phenotypic analysis of a Candida albicans mutant, characterized by a constitutive activation of the cAMP pathway due to deletion of PDE2, the gene encoding the high cAMP-affinity phosphodiesterase. Unlike wild-type strains, this mutant has an increased sensitivity to cell wall and membrane perturbing agents such as SDS and CFW, and antifungals such as amphotericin B and flucytosine. Moreover, the mutant is characterized by an altered sensitivity and a significantly reduced tolerance to fluconazole. The mutant's membrane has around 30% higher ergosterol content and the cell wall glucan was 22% lower than in the wild-type. These cell wall and membrane changes are manifested by a considerable reduction in the thickness of the cell wall, which in the mutant is on average 60-65 nm, compared to 80-85 nm in the wild-type strains as revealed by electron microscopy. These results suggest that constitutive activation of the cAMP pathway affects cell wall and membrane structure, and biosynthesis, not only in the model yeast S. cerevisiae but also in the human fungal pathogen C. albicans.
Jung
Won Hee
WH
Faculty of Life Sciences, Jackson's Mill, University of Manchester, PO Box 88, Sackville Street, Manchester M60 1QD, UK.
Warn
Peter
P
Ragni
Enrico
E
Popolo
Laura
L
Nunn
Christopher D
CD
Turner
Michael P
MP
Stateva
Lubomira
L
D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D002473:Cell Wall / Q000201:enzymology / Q000235:genetics / Q000648:ultrastructure; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D004875:Ergosterol / Q000378:metabolism; D015725:Fluconazole / Q000494:pharmacology; D005936:Glucans / Q000378:metabolism; D008566:Membranes / Q000201:enzymology / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D010727:Phosphoric Diester Hydrolases / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000378:metabolism
D000935:Antifungal Agents; D005936:Glucans; D012967:Sodium Dodecyl Sulfate; D015725:Fluconazole; D010727:Phosphoric Diester Hydrolases; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; C517275:PDE2A protein, human; D004875:Ergosterol