The fungal-specific Hda2 and Hda3 proteins regulate morphological switches in the human fungal pathogen Candida albicans
The fungal-specific Hda2 and Hda3 proteins regulate morphological switches in the human fungal pathogen Candida albicans
复制标题
真菌特异性 Hda2 和 Hda3 蛋白调节人类真菌病原体白色念珠菌的形态转换
DOI：
10.1101/340364
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Peterson M
中科院分区：
文献类型：
--
作者：
Peterson M
人类真菌病原体白色念珠菌每年造成数百万人感染。由于可用的抗真菌药物很少，耐药发生率不断增加，c。白色念珠菌感染正在急剧增加。形态开关，如白色不透明开关和酵母-菌丝开关，是ofC发育的关键。albicanspathogenic特征。赖氨酸去乙酰化酶作为形态转换的重要调节因子而出现。然而，针对赖氨酸去乙酰化酶进行药物开发是有问题的，因为真菌和人类蛋白质之间的高度同源性可能导致毒性。在这里，我们提供的证据表明，真菌特异性蛋白Hda2和Hda3与赖氨酸脱乙酰酶Hda1相互作用。通过结合表型分析和全基因组转录组分析，我们证明Hda2和Hda3控制c。albicansmorphological开关。在营养丰富的条件下，缺失hda2or hda3导致白色不透明开关主调控因子wor1适度过表达，开关频率增加。在诱导菌丝的条件下，hda2和hda3的缺失阻断了菌丝的发育。然而，hda2和hda3的缺失不影响体内菌丝的形成和毒力。我们认为Hda2和Hda3是开发联合治疗的抗真菌药物的良好靶点。
The human fungal pathogenCandida albicansis responsible for millions of infections annually. Due to the few available anti-fungal drugs and the increasing incidence of drug resistance, the number ofC. albicansinfections is dramatically increasing. Morphological switches, such as the white-opaque switch and the yeast-hyphae switch, are key for the development ofC. albicanspathogenic traits. Lysine deacetylases are emerging as important regulators of morphological switches. Yet, targeting lysine deacetylases for drug development is problematic due to the high homology between the fungal and human proteins that could result in toxicity. Here we provide evidence that the fungal specific proteins Hda2 and Hda3 interact with the lysine deacetylase Hda1. By combining phenotypic analyses with genome-wide transcriptome analyses, we demonstrate that Hda2 and Hda3 controlC. albicansmorphological switches. Under nutrient-rich conditions, deletion ofHDA2orHDA3leads to moderate overexpression of the master regulator of white-opaque switchingWOR1and increase switching frequency. Under hyphae inducing conditions, deletion ofHDA2andHDA3block hyphae development. However, deletion ofHDA2andHDA3does not affect hyphae-formation and virulencein vivo. We propose that Hda2 and Hda3 are good targets for the development of anti-fungal drugs to be used in combination therapy.
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影响因子：
30.3
作者：
Kadosh D;Lopez-Ribot JL
通讯作者：
Lopez-Ribot JL
影响因子：
4.5
作者：
Buscaino A;White SA;Houston DR;Lejeune E;Simmer F;de Lima Alves F;Diyora PT;Urano T;Bayne EH;Rappsilber J;Allshire RC
通讯作者：
Allshire RC
影响因子：
56.9
作者：
Staab, JF;Bradway, SD;Sundstrom, P
通讯作者：
Sundstrom, P
DOI：
10.1634/theoncologist.2017-0301
发表时间：
2018-05
期刊：
The oncologist
影响因子：
--
作者：
Tzogani K;van Hennik P;Walsh I;De Graeff P;Folin A;Sjöberg J;Salmonson T;Bergh J;Laane E;Ludwig H;Gisselbrecht C;Pignatti F
通讯作者：
Pignatti F
影响因子：
30.3
作者：
Lu Y;Su C;Solis NV;Filler SG;Liu H
通讯作者：
Liu H