RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in Candida albicans
RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in Candida albicans
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RTA2 参与白色念珠菌中钙调神经磷酸酶介导的唑类耐药性和鞘氨醇长链碱基释放
DOI：
10.1007/s00018-008-8409-3
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发表时间：
2009-01-01
影响因子：
8
通讯作者：
Jiang, Y. Y.
中科院分区：
文献类型：
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作者：
Jia, X. M.;Wang, Y.;Jiang, Y. Y.
据报道，钙调神经磷酸酶途径在白色念珠菌对唑类耐药性的产生中起着至关重要的作用。耗竭或异位过表达的RTA2分别增加或降低了白色念珠菌对氮唑类药物的敏感性。CaCl2诱导的野生型白色念珠菌中钙调神经磷酸酶途径的激活促进了对氮唑类药物的耐药性，而钙离子螯合剂(EGTA)、钙调神经磷酸酶抑制剂(FK506和环孢素A)和RTA2的缺失则阻断了CaCl2的促耐药作用。此外，我们发现RTA2以钙调神经磷酸酶依赖的方式上调。RtA2的缺失也使白念珠菌的细胞膜容易被氮唑破坏，而rtA2的过表达减弱了这种破坏作用。最后，RTA2的破坏导致二氢鞘氨醇(DHS)的积累增加，DHS是两个鞘脂长链碱基之一，通过减少DHS的释放。综上所述，我们的研究结果表明，rtA2参与了白念珠菌钙调神经磷酸酶介导的唑类耐药和狮身人面肌样长链碱基的释放。
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 Ca2+ 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.