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Cell Mol Life Sci. 2009 Jan;66(1):122-34. doi: 10.1007/s00018-008-8409-3.

RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in Candida albicans.

Author information

1
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.

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.

PMID:
19002381
DOI:
10.1007/s00018-008-8409-3
[Indexed for MEDLINE]

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