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首页> 外文期刊>Infection and immunity >Disruption of the Candida albicans TPS2 Gene Encoding Trehalose-6-Phosphate Phosphatase Decreases Infectivity without Affecting Hypha Formation
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Disruption of the Candida albicans TPS2 Gene Encoding Trehalose-6-Phosphate Phosphatase Decreases Infectivity without Affecting Hypha Formation

机译：编码白色海藻糖-6磷酸酶的白色念珠菌TPS2基因的破坏降低了感染力，而没有影响菌丝的形成。

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摘要

Deletion of trehalose-6-phosphate phosphatase, encoded by TPS2, in Saccharomyces cerevisiae results in accumulation of trehalose-6-phosphate (Tre6P) instead of trehalose under stress conditions. Since trehalose is an important stress protectant and Tre6P accumulation is toxic, we have investigated whether Tre6P phosphatase could be a useful target for antifungals in Candida albicans. We have cloned the C. albicans TPS2 (CaTPS2) gene and constructed heterozygous and homozygous deletion strains. As in S. cerevisiae, complete inactivation of Tre6P phosphatase in C. albicans results in 50-fold hyperaccumulation of Tre6P, thermosensitivity, and rapid death of the cells after a few hours at 44°C. As opposed to inactivation of Tre6P synthase by deletion of CaTPS1, deletion of CaTPS2 does not affect hypha formation on a solid glucose-containing medium. In spite of this, virulence of the homozygous deletion mutant is strongly reduced in a mouse model of systemic infection. The pathogenicity of the heterozygous deletion mutant is similar to that of the wild-type strain. CaTPS2 is a new example of a gene not required for growth under standard conditions but required for pathogenicity in a host. Our results suggest that Tre6P phosphatase may serve as a potential target for antifungal drugs. Neither Tre6P phosphatase nor its substrate is present in mammals, and assay of the enzymes is simple and easily automated for high-throughput screening.
机译：酿酒酵母中由 TPS2 编码的海藻糖6-磷酸磷酸酶的缺失导致了海藻糖-6-磷酸（Tre6P）的积累而不是海藻糖在应激条件下的积累。由于海藻糖是一种重要的应激保护剂，Tre6P的积累具有毒性，因此我们研究了Tre6P磷酸酶是否可以作为白色念珠菌中抗真菌药的有用靶标。我们已经克隆了 C。白色念珠菌TPS2 （ CaTPS2 ）基因，构建了杂合和纯合缺失菌株。如 S。 ， C中的Tre6P磷酸酶完全失活。白色念珠菌会导致Tre6P过度积累50倍，热敏性以及在44°C几个小时后细胞迅速死亡。与通过删除 CaTPS1 使Tre6P合酶失活相反，删除 CaTPS2 不会影响在含葡萄糖固体培养基上的菌丝形成。尽管如此，在全身感染的小鼠模型中，纯合缺失突变体的毒力仍大大降低。杂合缺失突变体的致病性与野生型菌株相似。 CaTPS2 是该基因在标准条件下不需要生长但在宿主中具有致病性所必需的基因的新示例。我们的结果表明，Tre6P磷酸酶可作为抗真菌药物的潜在靶标。 Tre6P磷酸酶及其底物均不存在于哺乳动物中，并且该酶的测定非常简单，并且易于自动化进行高通量筛选。

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