CaIPF14030 在白念珠菌唑类耐药发展过程中负调控细胞内 ATP 水平。
CaIPF14030 negatively modulates intracellular ATP levels during the development of azole resistance in Candida albicans.
机构信息
Department of Immunology, Tongji University School of Medicine, Shanghai, China.
出版信息
Acta Pharmacol Sin. 2011 Apr;32(4):512-8. doi: 10.1038/aps.2010.232.
AIM
Widespread and repeated use of azoles, particularly fluconazole, has led to the rapid development of azole resistance in Candida albicans. We investigated the role of CaIPF14030 during the development of azole resistance in C albicans.
METHODS
The expression of CaIPF14030 was measured by quantitative RT-PCR, and CaIPF14030 was disrupted by the hisG-URA3-hisG (URA-blaster) method. The sensitivity of C albicans to azoles was examined using a spot assay, and the intracellular ATP concentrations were measured by a luminometer.
RESULTS
CaIPF14030 expression in C albicans was up-regulated by Ca(2+) in a calcineurin-dependent manner, and the protein was overexpressed during the stepwise acquisition of azole resistance. However, disruption or ectopic overexpression of CaIPF14030 did not affect the sensitivity of C albicans to azoles. Finally, we demonstrated that disruption of CaIPF14030 significantly increased intracellular ATP levels, and overexpression significantly decreased intracellular ATP levels in C albicans.
CONCLUSION
CaIPF14030 may negatively modulate intracellular ATP levels during the development of azole resistance in C albicans.
目的
唑类药物，尤其是氟康唑的广泛和重复使用导致了白色念珠菌中唑类耐药性的迅速发展。我们研究了 CaIPF14030 在白色念珠菌唑类耐药性发展过程中的作用。
方法
通过定量 RT-PCR 测量 CaIPF14030 的表达，并通过 hisG-URA3-hisG（URA-blaster）方法破坏 CaIPF14030。通过点印迹法检测白色念珠菌对唑类药物的敏感性，并通过发光计测量细胞内 ATP 浓度。
结果
Ca(2+) 以钙调神经磷酸酶依赖性方式上调白色念珠菌中的 CaIPF14030 表达，并且在逐步获得唑类耐药性的过程中过度表达该蛋白。然而，CaIPF14030 的破坏或异位过表达并不影响白色念珠菌对唑类药物的敏感性。最后，我们证明破坏 CaIPF14030 可显著增加白色念珠菌中的细胞内 ATP 水平，而过表达则显著降低细胞内 ATP 水平。
结论
CaIPF14030 可能在白色念珠菌唑类耐药性发展过程中负调控细胞内 ATP 水平。
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