Calcineurin is essential for virulence in Candida albicans
Calcineurin is essential for virulence in Candida albicans
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DOI：
10.1128/iai.71.9.5344-5354.2003
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发表时间：
2003-09-01
影响因子：
3.1
通讯作者：
Morschhäuser, J
中科院分区：
文献类型：
--
作者：
Bader, T;Bodendorfer, B;Morschhäuser, J
钙调磷酸酶是一种保守的钙调蛋白激活的丝氨酸/苏氨酸特异性蛋白磷酸酶，其调节多种生理过程，例如，细胞周期进程、极化生长以及对盐和碱性pH胁迫的适应。在致病性酵母新生隐球菌中，钙调神经磷酸酶也是在37 ℃下生长和毒力所必需的。为了研究钙调神经磷酸酶是否在人类主要病原真菌白念珠菌的毒力中起作用，我们构建了C。白色念珠菌突变体，其中编码钙调磷酸酶催化亚基的CMP 1基因的两个等位基因均缺失。梭白色念珠菌Deltacmp 1突变体显示对升高的Na+、Li+和Mn 2+浓度和碱性pH的超敏反应，这些表型在相关酵母酿酒酵母中的钙调神经磷酸酶失活后已被描述。与S.酿酒酵母钙调神经磷酸酶突变体表现出对高Ca 2+浓度的敏感性降低，在缺失CMP 1后，在300 mM CaCl 2存在下，白色念珠菌的生长受到抑制，表明这两种酵母物种之间的钙调神经磷酸酶介导的细胞应答也存在差异。与C. neoformans中，钙调神经磷酸酶的失活并不引起C.白色念珠菌。此外，菌丝生长，一个重要的毒性属性的C。在各种诱导条件下，Deltacmp 1突变体中的白念珠菌，没有受损。然而，突变体的毒力在小鼠系统性念珠菌病模型中被强烈减弱，表明钙调神经磷酸酶信号传导对念珠菌的毒力至关重要。白色念珠菌。
Calcineurin is a conserved Ca2+-calmodulin-activated, serine/threonine-specific protein phosphatase that regulates a variety of physiological processes, e.g., cell cycle progression, polarized growth, and adaptation to salt and alkaline pH stresses. In the pathogenic yeast Cryptococcus neoformans, calcineurin is also essential for growth at 37degreesC and virulence. To investigate whether calcineurin plays a role in the virulence of Candida albicans, the major fungal pathogen of humans, we constructed C. albicans mutants in which both alleles of the CMP1 gene, encoding the calcineurin catalytic subunit, were deleted. The C. albicans Deltacmp1 mutants displayed hypersensitivity to elevated Na+, Li+, and Mn2+ concentrations and to alkaline pH, phenotypes that have been described after calcineurin inactivation in the related yeast Saccharomyces cerevisiae. Unlike S. cerevisiae calcineurin mutants, which exhibit reduced susceptibility to high Ca2+ concentrations, growth of C albicans was inhibited in the presence of 300 mM CaCl2 after the deletion of CMP1, demonstrating that there are also differences in calcineurin-mediated cellular responses between these two yeast species. In contrast to C. neoformans, inactivation of calcineurin did not cause temperature sensitivity in C. albicans. In addition, hyphal growth, an important virulence attribute of C. albicans, was not impaired in the Deltacmp1 mutants under a variety of inducing conditions. Nevertheless, the virulence of the mutants was strongly attenuated in a mouse model of systemic candidiasis, demonstrating that calcineurin signaling is essential for virulence in C. albicans.