Bee-safe peptidomimetic acaricides achieved by comparative genomics.
Bee-safe peptidomimetic acaricides achieved by comparative genomics.
复制标题
DOI：
10.1038/s41598-022-20110-0
复制
发表时间：
2022-10-14
影响因子：
4.6
通讯作者：
Park, Yoonseong
中科院分区：
文献类型：
--
作者：
Jindal, Vikas;Li, Daqi;Rault, Leslie C.;Fatehi, Soheila;Singh, Rupinder;Mating, Moritz;Zou, Ye;Ng, Ho-Leung;Kaczmarek, Krzysztof;Zabrocki, Janusz;Gui, Shunhua;Smagghe, Guy;Anderson, Troy D.;Nachman, Ronald J.;Park, Yoonseong
毁灭性的瓦螨（瓦螨）是蜜蜂的必然体外寄生虫，导致北美和世界各地的蜂群大量损失。用于减少瓦螨和预防蜂群疾病的传统杀螨剂数量有限，但面临广泛耐药性和低靶点选择性的挑战。在这里，我们提出了一种使用比较基因组学的生物理性方法，用于开发对蜜蜂安全的选择性杀螨剂，该杀螨剂针对由 proctolin 调节的瓦螨特异性神经肽能系统，而蜜蜂中缺乏 proctolin。 Proctolin 是一种高度保守的五肽 RYLPT (Arg-Tyr-Leu-Pro-Thr)，已知通过 G 蛋白偶联受体发挥作用，在节肢动物物种中引发肌动活性。总共 33 种不同的肽模拟物和肽变体在瓦螨前列腺素受体上进行了测试。配体对接模型和诱变研究揭示了 Proctolin 配体中核心芳香残基 Tyr2 的重要性。据观察，肽模拟物具有显着的口服毒性，导致瓦螨麻痹和死亡，而对蜜蜂没有观察到负面影响。我们已经证明，通过先进的基因组学信息识别的分类单元特异性生理目标为开发瓦螨选择性杀螨剂提供了机会，从而加快了转化过程。
The devastating Varroa mite (Varroa destructor Anderson and Trueman) is an obligatory ectoparasite of the honey bee, contributing to significant colony losses in North America and throughout the world. The limited number of conventional acaricides to reduce Varroa mites and prevent disease in honey bee colonies is challenged with wide-spread resistance and low target-site selectivity. Here, we propose a biorational approach using comparative genomics for the development of honey bee-safe and selective acaricides targeting the Varroa mite-specific neuropeptidergic system regulated by proctolin, which is lacking in the honey bee. Proctolin is a highly conserved pentapeptide RYLPT (Arg-Tyr-Leu-Pro-Thr) known to act through a G protein-coupled receptor to elicit myotropic activity in arthropod species. A total of 33 different peptidomimetic and peptide variants were tested on the Varroa mite proctolin receptor. Ligand docking model and mutagenesis studies revealed the importance of the core aromatic residue Tyr2 in the proctolin ligand. Peptidomimetics were observed to have significant oral toxicity leading to the paralysis and death of Varroa mites, while there were no negative effects observed for honey bees. We have demonstrated that a taxon-specific physiological target identified by advanced genomics information offers an opportunity to develop Varroa mite-selective acaricides, hence, expedited translational processes.
登录
查看更多内容
影响因子：
3.8
作者：
Aikins, Michael J.;Schooley, David A.;Park, Yoonseong
通讯作者：
Park, Yoonseong
影响因子：
3.7
作者：
De Smet L;Hatjina F;Ioannidis P;Hamamtzoglou A;Schoonvaere K;Francis F;Meeus I;Smagghe G;de Graaf DC
通讯作者：
de Graaf DC
影响因子：
2.2
作者：
Haber, Ariela, I;Steinhauer, Nathalie A.;vanEngelsdorp, Dennis
通讯作者：
vanEngelsdorp, Dennis
影响因子：
1.9
作者：
Fiandra, L.;Casartelli, M.;Giordana, B.
通讯作者：
Giordana, B.
影响因子：
2.2
作者：
Hinton, JM;Osborne, RH;Konopinska, D
通讯作者：
Konopinska, D