Deletion of <i>PDE2</i>, the gene encoding the high‐affinity cAMP phosphodiesterase, results in changes of the cell wall and membrane in <i>Candida albicans</i>

Yeast - Tập 22 Số 4 - Trang 285-294 - 2005
Won Hee Jung1, Peter Warn2, Enrico Ragni3, Laura Popolo3, Christopher D. Nunn4, Michael P. Turner4, Lubomira Stateva1
1Faculty of Life Sciences, Jackson's Mill, University of Manchester, PO Box 88, Sackville Street, Manchester M60 1QD, UK
2School of Medicine, University of Manchester, Stopford Building, Manchester M13 9PT, UK
3Dipartimento di Scienze Biomolecolari e Biotecnologie, Universita' degli Studi di Milano, 20133 Milano, Italy
4Cardiff School of Biosciences, Cardiff University, PO Box 915, Cardiff CF10 3TL, UK

Tóm tắt

AbstractA 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. Copyright © 2005 John Wiley & Sons, Ltd.

Từ khóa


Tài liệu tham khảo

10.1128/JCM.37.10.3332-3337.1999

10.1016/S0923-2508(03)00049-4

10.1046/j.1365-2958.2003.03692.x

10.1128/MCB.12.4.1764

10.1002/yea.905

10.1128/AAC.18.1.158

10.1002/clc.4960250603

10.1046/j.1469-0691.2000.00142.x

10.1093/genetics/134.3.717

10.1128/JB.182.9.2428-2437.2000

10.1128/AAC.39.12.2708

10.1016/S1369-5274(98)80087-8

10.1128/CMR.12.4.501

10.1093/nar/22.23.5011

10.1016/S0968-0004(97)01050-5

10.1111/j.1365-2672.1990.tb01564.x

10.1099/13500872-140-7-1533

10.1152/physiolgenomics.00139.2003

10.1002/cfg.415

10.1099/mic.0.26517-0

10.1128/AAC.44.6.1743-1744.2000

10.1016/S0014-5793(02)02704-7

10.1099/00221287-144-2-391

10.1128/MCB.7.10.3629

10.3109/10408418709104444

10.1128/AAC.47.10.3195-3201.2003

10.1128/jb.179.2.463-469.1997

10.1046/j.1365-2958.2003.03495.x

10.1073/pnas.83.24.9303

Sherman F, 1986, Methods in Yeast Genetics

10.1046/j.1365-2958.2003.03300.x

10.1139/m83-233

10.1099/00221287-146-9-2133

Vanden Bossche H, 1998, Antifungal drug resistance in pathogenic fungi, Med Mycol, 36, 119

10.1016/0014-5793(93)81071-7