1. RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in Candida albicans.
- Author
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Jia XM, Wang Y, Jia Y, Gao PH, Xu YG, Wang L, Cao YY, Cao YB, Zhang LX, and Jiang YY
- Subjects
- Biological Transport drug effects, Calcium pharmacology, Candida albicans genetics, Candida albicans metabolism, Candida albicans ultrastructure, Cell Membrane drug effects, Cell Membrane metabolism, Cell Membrane ultrastructure, Drug Resistance, Fungal genetics, Ergosterol biosynthesis, Fungal Proteins chemistry, Fungal Proteins genetics, Membrane Proteins chemistry, Membrane Proteins genetics, Microbial Sensitivity Tests, Rhodamines metabolism, Sphingosine analogs & derivatives, Sphingosine metabolism, Up-Regulation, Antifungal Agents pharmacology, Azoles pharmacology, Candida albicans drug effects, Drug Resistance, Fungal physiology, Fungal Proteins physiology, Membrane Proteins physiology
- Abstract
The calcineurin pathway has been reported to be essential for the development of azole resistance in Candida albicans. The depletion or ectopic over-expression of RTA2 increased or decreased susceptibility of C. albicans to azoles, respectively. CaCl(2)- induced activation of the calcineurin pathway in wildtype C. albicans promoted resistance to azoles, while the Ca(2+) chelator (EGTA), calcineurin inhibitors (FK506 and cyclosporin A) and the deletion of RTA2 blocked the resistance-promoting effects of CaCl(2). Furthermore, we found that RTA2 was up-regulated in a calcineurin-dependent manner. The depletion of RTA2 also made the cell membrane of C. albicans liable to be destroyed by azoles and RTA2 over-expression attenuated the destroying effects. Finally, the disruption of RTA2 caused an increased accumulation of dihydrosphingosine (DHS), one of the two sphingolipid long-chain bases, by decreasing release of DHS. In conclusion, our findings suggest that RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans.
- Published
- 2009
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