Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans.
Had1 Is Required for Cell Wall Integrity and Fungal Virulence in Cryptococcus neoformans.
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DOI：
10.1534/g3.117.300444
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发表时间：
2018-02-02
期刊：
影响因子：
--
通讯作者：
Park HS
中科院分区：
文献类型：
--
作者：
Jung WH;Son YE;Oh SH;Fu C;Kim HS;Kwak JH;Cardenas ME;Heitman J;Park HS
钙调神经磷酸酶调节环境应激生存和人类真菌病原体新生隐球菌的毒力。此前，我们确定了44种可能的钙调神经磷酸酶底物，并提出在新生隐球菌中，钙调神经磷酸酶途径被分支来调节包括Crz1、Pbp1和Puf4在内的靶点。在本研究中，我们对HAD1进行了鉴定，它是一种可能的钙调神经磷酸酶底物，属于普遍保守的卤酸脱卤酶β-磷酸葡萄糖变位酶蛋白超家族。HAD1∆突变体的生长在38°或更高时受到影响。此外，HAD1∆突变体对包括刚果红和硫代氟白在内的细胞壁干扰剂以及内质网应激诱导剂二硫苏糖醇表现出更高的敏感性。毒力研究表明，在小鼠吸入性感染模型中，与野生型毒株相比，HAD1突变导致毒力减弱。遗传上位性分析表明，Had1和锌指转录因子Crz1在协调逆境生存和真菌毒力的平行途径中发挥作用。总体而言，我们的结果表明，Had1是耐热性、细胞壁完整性和新月弯曲菌毒力的关键调节因子。
Calcineurin modulates environmental stress survival and virulence of the human fungal pathogen Cryptococcus neoformans. Previously, we identified 44 putative calcineurin substrates, and proposed that the calcineurin pathway is branched to regulate targets including Crz1, Pbp1, and Puf4 in C. neoformans. In this study, we characterized Had1, which is one of the putative calcineurin substrates belonging to the ubiquitously conserved haloacid dehalogenase β-phosphoglucomutase protein superfamily. Growth of the had1∆ mutant was found to be compromised at 38° or higher. In addition, the had1∆ mutant exhibited increased sensitivity to cell wall perturbing agents, including Congo Red and Calcofluor White, and to an endoplasmic reticulum stress inducer dithiothreitol. Virulence studies revealed that the had1 mutation results in attenuated virulence compared to the wild-type strain in a murine inhalation infection model. Genetic epistasis analysis revealed that Had1 and the zinc finger transcription factor Crz1 play roles in parallel pathways that orchestrate stress survival and fungal virulence. Overall, our results demonstrate that Had1 is a key regulator of thermotolerance, cell wall integrity, and virulence of C. neoformans.
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影响因子：
4.5
作者：
Chow EW;Clancey SA;Billmyre RB;Averette AF;Granek JA;Mieczkowski P;Cardenas ME;Heitman J
通讯作者：
Heitman J
影响因子：
11.4
作者：
Cruz, MC;Fox, DS;Heitman, J
通讯作者：
Heitman, J
DOI：
10.1016/j.bbrc.2003.09.174
发表时间：
2003-11-28
影响因子：
3.1
作者：
Feske, S;Okamura, H;Rao, A
通讯作者：
Rao, A
影响因子：
3.1
作者：
Cox, GM;Mukherjee, J;Perfect, JR
通讯作者：
Perfect, JR
影响因子：
4.8
作者：
Danielsen, Andreas A.;Parker, Mark D.;Boedtkjer, Ebbe
通讯作者：
Boedtkjer, Ebbe