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了解你的敌人——粘孢子虫转录组揭示了针对鲑科鱼类增生性肾病的潜在药物靶点。

Know your enemy - transcriptome of myxozoan reveals potential drug targets against proliferative kidney disease in salmonids.

机构信息

Department of Biology, University of Turku, FI-20014, Finland.

Department of Aquaculture and Fish Biology, Hólar University, Saudárkrókur, Iceland.

出版信息

Parasitology. 2021 May;148(6):726-739. doi: 10.1017/S003118202100010X. Epub 2021 Jan 22.

Abstract

The myxozoan Tetracapsuloides bryosalmonae is a widely spread endoparasite that causes proliferative kidney disease (PKD) in salmonid fish. We developed an in silico pipeline to separate transcripts of T. bryosalmonae from the kidney tissue of its natural vertebrate host, brown trout (Salmo trutta). After stringent filtering, we constructed a partial transcriptome assembly T. bryosalmonae, comprising 3427 transcripts. Based on homology-restricted searches of the assembled parasite transcriptome and Atlantic salmon (Salmo salar) proteome, we identified four protein targets (Endoglycoceramidase, Legumain-like protease, Carbonic anhydrase 2, Pancreatic lipase-related protein 2) for the development of anti-parasitic drugs against T. bryosalmonae. Earlier work of these proteins on parasitic protists and helminths suggests that the identified anti-parasitic drug targets represent promising chemotherapeutic candidates also against T. bryosalmonae, and strengthen the view that the known inhibitors can be effective in evolutionarily distant organisms. In addition, we identified differentially expressed T. bryosalmonae genes between moderately and severely infected fish, indicating an increased abundance of T. bryosalmonae sporogonic stages in fish with low parasite load. In conclusion, this study paves the way for future genomic research in T. bryosalmonae and represents an important step towards the development of effective drugs against PKD.

摘要

微孢子虫 Tetracapsuloides bryosalmonae 是一种广泛传播的内寄生虫,会引起鲑鱼的增殖性肾病(PKD)。我们开发了一种计算机管道,以从其自然脊椎动物宿主(褐鳟)的肾脏组织中分离出 T. bryosalmonae 的转录本。经过严格过滤,我们构建了 T. bryosalmonae 的部分转录组组装,包含 3427 个转录本。基于对寄生虫转录组和大西洋鲑鱼(Salmo salar)蛋白质组的同源性限制搜索,我们鉴定了四个蛋白质靶标(内糖苷酶、类 Legumain 蛋白酶、碳酸酐酶 2、胰脂肪酶相关蛋白 2),用于开发针对 T. bryosalmonae 的抗寄生虫药物。这些蛋白质在寄生原生动物和蠕虫上的早期研究表明,鉴定出的抗寄生虫药物靶标代表了针对 T. bryosalmonae 的有前途的化学治疗候选物,并加强了这样的观点,即已知的抑制剂在进化上遥远的生物体中也可能有效。此外,我们还鉴定了中度和重度感染鱼类之间差异表达的 T. bryosalmonae 基因,表明在寄生虫负荷低的鱼类中,T. bryosalmonae 有性生殖阶段的丰度增加。总之,这项研究为 T. bryosalmonae 的未来基因组研究铺平了道路,并代表了开发针对 PKD 的有效药物的重要一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/119c/8056827/31d1fcb19f10/S003118202100010X_figAb.jpg

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