The Ess1 prolyl isomerase is dispensable for growth but required for virulence in Cryptococcus neoformans.
The Ess1 prolyl isomerase is dispensable for growth but required for virulence in Cryptococcus neoformans.
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Ess1 脯氨酰异构酶对于新型隐球菌的生长不是必需的，但对于其毒力却是必需的。
DOI：
10.1099/mic.0.27786-0
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Hanes,StevenD
中科院分区：
文献类型：
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作者：
Ren,Ping;Rossettini,Anne;Chaturvedi,Vishnu;Hanes,StevenD
新生隐球菌是一种重要的人类真菌病原菌，也是研究真菌致病机理的模型。新生隐球菌含有几个编码肽基-脯氨基顺式/转移酶(PPIase)的基因，这些酶催化靶蛋白折叠和构象的变化。目前已鉴定出三类不同的PPIase：亲环素、FK506结合蛋白(FKBPs)和小球蛋白。本文报道了ESS1的克隆和特性，它被认为是第一个(也可能是唯一的)PPIase Inc.新形态主义者。结果表明，从C。酿酒酵母ESS1在结构和功能上与酿酒酵母ESS1同源，ESS1编码一种重要的PPIase，与RNA聚合酶II相互作用，并在转录中发挥作用。Inc.新生杆菌，ESS1是生长、单倍体结实和被果形成所必需的。然而，在隐球菌病的小鼠模型中，ESS1是毒力所必需的。毒力的丧失可能是由于观察到的突变株的黑色素和尿素酶产生的缺陷，或者是由于迄今尚未确定的毒力基因的转录缺陷。Ess1不是Ess1 Essential Inc.Neformans认为，在这种有机体中，它的一些功能可能被其他Pro异构酶所包含，特别是亲环素Cpa1或Cpa2。这一发现支持这一发现，即没有1个突变体对环孢素高度敏感，因此可能是一种有用的有机体，可以用来研究不同家族的Pro异构酶之间的串扰。
Cryptococcus neoformansis an important human fungal pathogen that also serves as a model for studies of fungal pathogenesis.C. neoformanscontains several genes encoding peptidyl-prolylcis/transisomerases (PPIases), enzymes that catalyse changes in the folding and conformation of target proteins. Three distinct classes of PPIases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. This paper reports the cloning and characterization ofESS1, which is believed to be the first (and probably only) parvulin-class PPIase inC. neoformans. It is shown thatESS1fromC. neoformansis structurally and functionally homologous toESS1fromSaccharomyces cerevisiae, which encodes an essential PPIase that interacts with RNA polymerase II and plays a role in transcription. InC. neoformans,ESS1was found to be dispensable for growth, haploid fruiting and capsule formation. However,ESS1was required for virulence in a murine model of cryptococcosis. Loss of virulence might have been due to the defects in melanin and urease production observed iness1mutants, or to defects in transcription of as-yet-unidentified virulence genes. The fact that Ess1 is not essential inC. neoformanssuggests that, in this organism, some of its functions might be subsumed by other prolyl isomerases, in particular, cyclophilins Cpa1 or Cpa2. This is supported by the finding thatess1mutants were hypersensitive to cyclosporin A.C. neoformansmight therefore be a useful organism in which to investigate crosstalk among different families of prolyl isomerases.