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美洲锥虫 Trypanosoma rangeli 和 Trypanosoma cruzi 之间精氨酸激酶的差异表达和活性。

Differential expression and activity of arginine kinase between the American trypanosomatids Trypanosoma rangeli and Trypanosoma cruzi.

机构信息

Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

出版信息

Exp Parasitol. 2021 Nov;230:108159. doi: 10.1016/j.exppara.2021.108159. Epub 2021 Sep 23.

DOI:10.1016/j.exppara.2021.108159
PMID:34563508
Abstract

Trypanosoma rangeli is a non-virulent hemoflagellate parasite infecting humans, wild and domestic mammals in Central and Latin America. The share of genotypic, phenotypic, and biological similarities with the virulent, human-infective T. cruzi and T. brucei, allows comparative studies on mechanisms of pathogenesis. In this study, investigation of the T. rangeli Arginine Kinase (TrAK) revealed two highly similar copies of the AK gene in this taxon, and a distinct expression profile and activity between replicative and infective forms. Although TrAK expression seems stable during epimastigotes growth, the enzymatic activity increases during the exponential growth phase and decreases from the stationary phase onwards. No differences were observed in activity or expression levels of TrAK during in vitro differentiation from epimastigotes to infective forms, and no detectable AK expression was observed for blood trypomastigotes. Overexpression of TrAK by T. rangeli showed no effects on the in vitro growth pattern, differentiation to infective forms, or infectivity to mice and triatomines. Although differences in TrAK expression and activity were observed among T. rangeli strains from distinct genetic lineages, our results indicate an up-regulation during parasite replication and putative post-translational myristoylation of this enzyme. We conclude that up-regulation of TrAK activity in epimastigotes appears to improve proliferation fitness, while reduced TrAK expression in blood trypomastigotes may be related to short-term and subpatent parasitemia in mammalian hosts.

摘要

冈比亚锥虫是一种非致病的血鞭毛原生动物,感染中美洲和拉丁美洲的人类、野生动物和家畜。它与致病的、感染人类的克氏锥虫和布氏锥虫在基因型、表型和生物学上有很大的相似性,这使得人们能够对发病机制进行比较研究。在这项研究中,对冈比亚锥虫精氨酸激酶(TrAK)的研究表明,该分类群中有两个高度相似的 AK 基因拷贝,以及在复制和感染形式之间存在明显不同的表达谱和活性。尽管 TrAK 的表达在锥形体的生长过程中似乎是稳定的,但酶活性在指数生长阶段增加,并从静止阶段开始下降。在体外从锥形体到感染形式的分化过程中,TrAK 的活性或表达水平没有差异,也没有检测到血液锥虫体中的 AK 表达。冈比亚锥虫的 TrAK 过表达对体外生长模式、向感染形式的分化或对小鼠和三锥虫的感染性没有影响。尽管不同遗传谱系的冈比亚锥虫菌株之间观察到 TrAK 表达和活性的差异,但我们的结果表明,该酶在寄生虫复制过程中上调,并且可能发生翻译后豆蔻酰化。我们得出结论,在锥形体中 TrAK 活性的上调似乎改善了增殖适应性,而血液锥虫体中 TrAK 表达的降低可能与哺乳动物宿主中的短期和亚潜伏性寄生虫血症有关。

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