Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway.
Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway.
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DOI：
10.1016/j.fgb.2012.02.001
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发表时间：
2012-04
影响因子：
3
通讯作者：
Bahn, Yong-Sun
中科院分区：
文献类型：
--
作者：
Jung, Kwang-Woo;Strain, Anna K.;Nielsen, Kirsten;Jung, Kwang-Hwan;Bahn, Yong-Sun
维持阳离子稳态对于所有生物体在其生物生态位中的生存至关重要。它对人类病原真菌在宿主中的生存也很重要，其中阳离子浓度和pH值将根据不同的解剖部位而变化。然而，不同的阳离子转运蛋白和离子通道在真菌病原体毒力中的确切作用仍然是难以捉摸的。在这项研究中，我们的功能特点ENA 1和NHA 1，编码一个假定的Na+/ATP酶和Na+/H+反向转运蛋白，分别在新型隐球菌，一种担子菌真菌病原体，导致致命的脑膜脑炎。NHA 1和ENA 1的表达主要以Hog 1依赖的方式响应于盐和渗透压休克而被诱导。ena 1，nha 1和ena 1 nha 1突变体的表型分析显示，Ena 1控制细胞水平的有毒阳离子，如Na+和Li+，而Ena 1和Nha 1都是重要的控制毒性较低的K+离子。在碱性条件下，Ena 1是高度诱导的，在低水平的Na+或K+盐的存在下生长所需的，Nha 1在K+胁迫下的生存中发挥作用。相反，Nha 1，而不是Ena 1，是在酸性条件下（pH 4.5）在高K+胁迫下生存所必需的。此外，Ena 1和Nha 1需要维持质膜电位和稳定性，这似乎调节抗真菌药物的敏感性。ENA 1和NHA 1的扰动增强了胶囊的产生和黑色素的合成。而Nha 1的毒力较弱。虽然Ena 1是必不可少的。总之，Ena 1和Nha 1在C.提示这些转运蛋白可能是治疗隐球菌病的新的抗真菌药物靶点。
Maintenance of cation homeostasis is essential for survival of all living organisms in their biological niches. It is also important for the survival of human pathogenic fungi in the host, where cation concentrations and pH will vary depending on different anatomical sites. However, the exact role of diverse cation transporters and ion channels in virulence of fungal pathogens remains elusive. In this study we functionally characterized ENA1 and NHA1, encoding a putative Na+/ATPase and Na+/H+ antiporter, respectively, in Cryptococcus neoformans, a basidiomycete fungal pathogen which causes fatal meningoencephalitis. Expression of NHA1 and ENA1 is induced in response to salt and osmotic shock mainly in a Hog1-dependent manner. Phenotypic analysis of the ena1, nha1, and ena1 nha1 mutants revealed that Ena1 controls cellular levels of toxic cations, such as Na+ and Li+ whereas both Ena1 and Nha1 are important for controlling less toxic K+ ions. Under alkaline conditions, Ena1 was highly induced and required for growth in the presence of low levels of Na+ or K+ salt and Nha1 played a role in survival under K+ stress. In contrast, Nha1, but not Ena1, was essential for survival at acidic conditions (pH 4.5) under high K+ stress. In addition, Ena1 and Nha1 were required for maintenance of plasma membrane potential and stability, which appeared to modulate antifungal drug susceptibility. Perturbation of ENA1 and NHA1 enhanced capsule production and melanin synthesis. However, Nha1 was dispensable for virulence of C. neoformans although Ena1 was essential. In conclusion, Ena1 and Nha1 play redundant and discrete roles in cation homeostasis, pH regulation, membrane potential, and virulence in C. neoformans, suggesting that these transporters could be novel antifungal drug targets for treatment of cryptococcosis.
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影响因子：
3.3
作者：
Bahn, YS;Kojima, K;Heitman, J
通讯作者：
Heitman, J
影响因子：
2.8
作者：
Benito, B;Garciadeblás, B;Rodríguez-Navarro, A
通讯作者：
Rodríguez-Navarro, A
影响因子：
3.2
作者：
Kinclova-Zimmermannova, Olga;Gaskova, Dana;Sychrova, Hana
通讯作者：
Sychrova, Hana
影响因子：
3
作者：
Jung, Kwang-Woo;Kim, Seo-Young;Okagaki, Laura H.;Nielsen, Kirsten;Bahn, Yong-Sun
通讯作者：
Bahn, Yong-Sun
影响因子：
3.2
作者：
Krauke, Yannick;Sychrova, Hana
通讯作者：
Sychrova, Hana