The contribution of the White Collar complex to Cryptococcus neoformans virulence is independent of its light-sensing capabilities.

The contribution of the White Collar complex to Cryptococcus neoformans virulence is independent of its light-sensing capabilities.
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DOI:
10.1016/j.fgb.2018.09.008
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发表时间:
2018-12
期刊:
Fungal genetics and biology : FG & B
影响因子:
--
通讯作者:
Idnurm A
Idnurm A
中科院分区:
其他
文献类型:
--
作者:
Zhu P;Idnurm A

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在许多真菌中,白色项圈复合体负责感知光线并传递信号。在新生隐球菌和隐球菌C.该复合物涉及保护免受紫外线(UV)的损害,抑制响应于光的交配,并且也是毒力所需的。Bwc 1光受体对毒力的作用机制尚不清楚。本研究以C.用三种形式的BWC 1基因(野生型、BWC 1C 605 A或BWC 1C 605 S)转化新生儿,其中后两种在与黄素发色团相互作用的光-氧-电压(LOV)结构域内具有被丙氨酸或丝氨酸取代的保守半胱氨酸残基。bwc 1 + BWC 1菌株补充了紫外线敏感性和在光照下的交配抑制。bwc 1 + BWC 1C 605 A和bwc 1 + BWC 1C 605 S菌株的任一表型都没有完全互补,表明这些BWC 1等位基因损害了具有它们的菌株的光响应。转录分析表明,突变菌株(bwc 1 + BWC 1C 605 A和bwc 1 + BWC 1C 605 S)都没有显示出在野生型菌株中发生的光诱导的HEM 15和UVE 1基因表达模式。这些结果表明,Bwc 1的LOV结构域中保守的黄素结合位点是C.新人类与光反应缺陷相反,野生型、bwc 1 + BWC 1、bwc 1 + BWC 1C 605 A和bwc 1 + BWC 1C 605 S菌株的毒性相同,而bwc 1敲除突变体的毒性较低。此外,在接种前将菌株预先暴露于光对感染的结果没有影响。这些发现定义了真菌中白色领复合体的功能划分,在C. Bwc 1在毒力中的作用不依赖于光感。
The White Collar complex is responsible for sensing light and transmitting that signal in many fungal species. In Cryptococcus neoformans and C. deneoformans the complex is involved in protection against damage from ultraviolet (UV) light, repression of mating in response to light, and is also required for virulence. The mechanism by which the Bwc1 photoreceptor contributes to virulence is unknown. In this study, a bwc1 deletion mutant of C. neoformans was transformed with three versions of the BWC1 gene, the wild type, BWC1C605A or BWC1C605S, in which the latter two have the conserved cysteine residue replaced with either alanine or serine within the light-oxygen-voltage (LOV) domain that interacts with the flavin chromophore. The bwc1+BWC1 strain complemented the UV sensitivity and the repression of mating in the light. The bwc1+BWC1C605A and bwc1+BWC1C605S strains were not fully complemented for either of the phenotypes, indicating that these BWC1 alleles impair the light responses for strains with them. Transcript analysis showed that neither of the mutated strains (bwc1+BWC1C605A and bwc1+BWC1C605S) showed the light-inducible expression pattern of the HEM15 and UVE1 genes as occurs in the wild type strain. These results indicate that the conserved flavin-binding site in the LOV domain of Bwc1 is required for sensing and responding to light in C. neoformans. In contrast to defects in light responses, the wild type, bwc1+BWC1, bwc1+BWC1C605A and bwc1+BWC1C605S strains were equally virulent, whereas the bwc1 knock out mutant was less virulent. Furthermore, pre-exposure of the strains to light prior to inoculation had no influence on the outcome of infection. These findings define a division in function of the White Collar complex in fungi, in that in C. neoformans the role of Bwc1 in virulence is independent of light sensing.
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