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- Title
RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in Candida albicans.
- Authors
Jia, X. M.; Wang, Y.; Jia, Y.; Gao, P. H.; Xu, Y. G.; Wang, L.; Cao, Y. Y.; Cao, Y. B.; Zhang, L. X.; Jiang, Y. Y.
- 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. CaCl2- 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 CaCl2. 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.
- Subjects
AZOLES; CANDIDA albicans; CANDIDA; IRON chelates; CELL membranes
- Publication
Cellular & Molecular Life Sciences, 2009, Vol 66, Issue 1, p122
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-008-8409-3