Cryptococcus neoformans STE12alpha regulates virulence but is not essential for mating.

Cryptococcus neoformans STE12alpha regulates virulence but is not essential for mating.
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DOI:
10.1084/jem.191.5.871
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发表时间:
2000-03-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Kwon-Chung KJ
Kwon-Chung KJ
中科院分区:
其他
文献类型:
--
作者:
Chang YC;Wickes BL;Miller GF;Penoyer LA;Kwon-Chung KJ

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新型隐球菌STE12α基因是酿酒酵母STE12的同源物,仅存在于交配型(MAT)α细胞中。在酿酒酵母中,STE12 是交配和细丝形成所必需的。在新型隐球菌中,长丝琼脂上的单倍体子实体需要 STE12α。然而,当存在聚集生长的 MATa 菌株时,形成菌丝的能力不受 STE12α 删除的影响。此外,ste12α 破坏株与 MATa 菌株交配时具有可育性,尽管交配频率降低。最重要的是,血清型 D 株的 ste12α 破坏株的毒力在小鼠模型中显着降低。当 ste12α 基因座通过共转化与野生型等位基因重建时,毒力恢复。组织病理学分析表明,与感染 STE12α 细胞的小鼠相比,感染 ste12α 细胞的小鼠脑膜中酵母细胞的荚膜尺寸减小,囊性病变不那么严重,并且免疫反应更强。使用报告基因构建体,我们发现 STE12α 控制已知与毒力有关的几种表型的表达,例如荚膜和黑色素的产生。这些结果表明,新生隐球菌的交配类型和毒力之间存在明显的分子联系。
The Cryptococcus neoformans STE12α gene, a homologue of Saccharomyces cerevisiae STE12, exists only in mating type (MAT)α cells. In S. cerevisiae, STE12 was required for mating and filament formation. In C. neoformans, haploid fruiting on filament agar required STE12α. The ability to form hyphae, however, was not affected by deletion of STE12α when convergently growing MATa strains were present. Furthermore, ste12α disruptants were fertile when mated with MATa strains, albeit with reduced mating frequency. Most importantly, the virulence of a ste12α disruptant of serotype D strain was significantly reduced in a mouse model. When the ste12α locus was reconstituted with the wild-type allele by cotransformation, virulence was restored. Histopathological analysis demonstrated a reduction in capsular size of yeast cells, less severe cystic lesions, and stronger immune responses in meninges of mice infected with ste12α cells than those of mice infected with STE12α cells. Using reporter gene constructs, we found that STE12α controls the expression of several phenotypes known to be involved in virulence, such as capsule and melanin production. These results demonstrate a clear molecular link between mating type and virulence in C. neoformans.
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