Contribution of VMA5 to vacuolar function, stress response, ion homeostasis and autophagy in Candida albicans.
Contribution of VMA5 to vacuolar function, stress response, ion homeostasis and autophagy in Candida albicans.
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DOI：
10.2217/fmb-2017-0029
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发表时间：
2017-09
影响因子：
3.1
通讯作者：
Kai Zhang;Chang Jia;Qilin Yu;Chenpeng Xiao;Yijie Dong;Meng Zhang;Dan Zhang;Qiang Zhao;Biao Zhang;Mingchun Li
中科院分区：
文献类型：
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作者：
Kai Zhang;Chang Jia;Qilin Yu;Chenpeng Xiao;Yijie Dong;Meng Zhang;Dan Zhang;Qiang Zhao;Biao Zhang;Mingchun Li
目的V-ATPase是真核生物中一种保守的多亚单位酶，调节多种细胞反应。本研究旨在阐明Vma5在空泡功能、氧化应激反应、钙稳态、自噬和毒力中的作用。材料与方法用聚合酶链式反应介导的同源重组技术获得Vma5Δ/Δ突变体。通过一系列生化和系统感染方法对Vma5的功能进行研究。结果VMA5基因的干扰可导致细胞生长抑制、空泡功能障碍、钙稳态紊乱和钙相关氧化应激反应受抑。此外，它的缺失导致自噬完成和菌丝发育的缺陷，导致白色念珠菌的毒力减弱。结论我们的研究结果为了解白色念珠菌的V-ATPase功能提供了新的思路，并为抗真菌药物的开发提供了一个潜在的候选药物。
AIM V-ATPase is a conservative multi-subunit enzyme in eukaryotes and modulates several cellular responses. This study aimed to illustrate the roles of Vma5 in vacuolar function, oxidative stress response, calcium homeostasis, autophagy and virulence. MATERIALS & METHODS The vma5Δ/Δ mutant was obtained using PCR-mediated homologous recombination. The functions of Vma5 were investigated by a series of biochemical and systemic infection methods. RESULTS Disruption of VMA5 led to growth inhibition, vacuolar dysfunction, disturbance of calcium homeostasis and inhibition of calcium-related oxidative stress response. Furthermore, its deletion caused defects in autophagy completion and hyphal development, and resulted in attenuated Candida albicans virulence. CONCLUSION Our findings provide new insights into V-ATPase functions in C. albicans, and reveal a potential candidate for development of antifungal drugs.