Mutation of the CgPDR16 gene attenuates azole tolerance and biofilm production in pathogenic Candida glabrata
Article first published online: 27 AUG 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Volume 30, Issue 10, pages 403–414, October 2013
How to Cite
Culakova, H., Dzugasova, V., Perzelova, J., Gbelska, Y. and Subik, J. (2013), Mutation of the CgPDR16 gene attenuates azole tolerance and biofilm production in pathogenic Candida glabrata. Yeast, 30: 403–414. doi: 10.1002/yea.2978
- Issue published online: 7 OCT 2013
- Article first published online: 27 AUG 2013
- Accepted manuscript online: 12 AUG 2013 07:36AM EST
- Manuscript Accepted: 7 AUG 2013
- Manuscript Revised: 23 JUL 2013
- Manuscript Received: 5 JUN 2013
- multidrug resistance;
- Candida glabrata;
- rhodamine 6G
The PDR16 gene encodes the homologue of Sec14p, participating in protein secretion, regulation of lipid synthesis and turnover in vivo and acting as a phosphatidylinositol transfer protein in vitro. This gene is also involved in the regulation of multidrug resistance in Saccharomyces cerevisiae and pathogenic yeasts. Here we report the results of functional analysis of the CgPDR16 gene, whose mutation has been previously shown to enhance fluconazole sensitivity in Candida glabrata mutant cells. We have cloned the CgPDR16 gene, which was able to complement the pdr16Δ mutation in both C. glabrata and S. cerevisiae. Along with fluconazole, the pdr16Δ mutation resulted in increased susceptibility of mutant cells to several azole antifungals without changes in sensitivity to polyene antibiotics, cycloheximide, NQO, 5-fluorocytosine and oxidants inducing the intracellular formation of reactive oxygen species. The susceptibility of the pdr16Δ mutant strain to itraconazole and 5-fluorocytosine was enhanced by CTBT [7-chlorotetrazolo(5,1-c)benzo(1,2,4)triazine] inducing oxidative stress. The pdr16Δ mutation increased the accumulation of rhodamine 6G in mutant cells, decreased the level of itraconazole resistance caused by gain-of-function mutations in the CgPDR1 gene, and reduced cell surface hydrophobicity and biofilm production. These results point to the pleiotropic phenotype of the pdr16Δ mutant and support the role of the CgPDR16 gene in the control of drug susceptibility and virulence in the pathogenic C. glabrata. Copyright © 2013 John Wiley & Sons, Ltd.