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从基因表达数据中挖掘新的药物靶点和疫苗候选物,以对抗牛蜱,即 Rhipicephalus microplus。

Mining gene expression data for rational identification of novel drug targets and vaccine candidates against the cattle tick, Rhipicephalus microplus.

机构信息

Department of Biochemistry, Genetics and Microbiology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, Gauteng, South Africa.

DNA Microarray Laboratory, Department of Plant Sciences, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, Gauteng, South Africa.

出版信息

Exp Appl Acarol. 2023 Oct;91(2):291-317. doi: 10.1007/s10493-023-00838-8. Epub 2023 Sep 27.

Abstract

Control of complex parasites via vaccination remains challenging, with the current combination of vaccines and small drugs remaining the choice for an integrated control strategy. Studies conducted to date, are providing evidence that multicomponent vaccines will be needed for the development of protective vaccines against endo- and ectoparasites, though multicomponent vaccines require an in-depth understanding of parasite biology which remains insufficient for ticks. With the rapid development and spread of acaricide resistance in ticks, new targets for acaricide development also remains to be identified, along with novel targets that can be exploited for the design of lead compounds. In this study, we analysed the differential gene expression of Rhipicephalus microplus ticks that were fed on cattle vaccinated with a multi-component vaccine (Bm86 and 3 putative Bm86-binding proteins). The data was scrutinised for the identification of vaccine targets, small drug targets and novel pathways that can be evaluated in future studies. Limitations associated with targeting novel proteins for vaccine and/or drug design is also discussed and placed into the context of challenges arising when targeting large protein families and intracellular localised proteins. Lastly, this study provide insight into how Bm86-based vaccines may reduce successful uptake and digestion of the bloodmeal and overall tick fecundity.

摘要

通过疫苗控制复杂寄生虫仍然具有挑战性,目前疫苗和小药物的组合仍然是综合控制策略的选择。迄今为止进行的研究提供了证据,表明需要多组分疫苗来开发针对内寄生虫和外寄生虫的保护性疫苗,尽管多组分疫苗需要深入了解寄生虫生物学,但这对于蜱虫来说仍然不够。随着蜱虫杀螨剂耐药性的迅速发展和传播,也需要确定新的杀螨剂开发靶点,以及可用于设计先导化合物的新靶点。在这项研究中,我们分析了接种多组分疫苗(Bm86 和 3 种假定的 Bm86 结合蛋白)的牛身上寄生的 Rhipicephalus microplus 蜱的差异基因表达。对数据进行了仔细分析,以确定疫苗靶点、小分子药物靶点和可在未来研究中评估的新途径。还讨论了针对新型蛋白质进行疫苗和/或药物设计的局限性,并将其置于针对大型蛋白质家族和细胞内定位蛋白质时出现的挑战的背景下。最后,这项研究深入了解了基于 Bm86 的疫苗如何减少血液摄入和消化的成功率以及整体蜱的繁殖力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a57e/10562289/288aac1c5217/10493_2023_838_Fig1_HTML.jpg

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