Expression of transporter genes in anthelmintic resistant isolates of Haemonchus contortus.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-08-16 eCollection Date: 2024-01-01 DOI:10.1590/1678-4685-GMB-2023-0350
Janaelia Ferreira Vasconcelos Rodrigues, Jessica Maria Leite Dos Santos, Gracielle Araújo Frota, Luiz da Silva Vieira, Marcel Teixeira, Magaly Sales Monteiro, Jomar Patrício Monteiro
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Abstract

ATP-binding cassette (ABC) transporters, including P-glycoproteins (PGP), have been implicated in drug resistance in different organisms including Haemonchus contortus. This study confirmed the resistance status of H. contortus isolates selected for ivermectin (IVM) and oxfendazole (OXF) resistances using the fecal egg count reduction test and evaluated the gene expression of seven ABC transporters using RT-qPCR for two biological scenarios: the effect of selection for anthelmintic resistance and the effect of drug exposure on gene expression. Gene expression results showed that selection for IVM resistance led to the significant upregulation of Hco-pgp-9a (1.5-fold), Hco-pgp-11 (3-fold) and Hco-haf-9 (1.5-fold) (p < 0.05). Similarly, selection for OXF resistance led to the significant upregulation of Hco-pgp-9a (3-fold), Hco-pgp-11 (4-fold) and Hco-haf-9 (2-fold) when comparing with the unselected ISE isolate (p < 0.05). Exposure of selected isolates to anthelmintics lead to no significant upregulation of the studied transporter genes. We also observed instances where there was strong intragroup variation regarding samples originating from parasites obtained from different individual hosts pointing that the interactions of the animal host with the tested anthelmintics may also play a role in the expression of the studied nematode genes.

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对驱虫药有抗药性的线虫分离株中转运体基因的表达。
ATP结合盒(ABC)转运体,包括P-糖蛋白(PGP),与包括轮虫在内的不同生物的耐药性有关。本研究利用粪便卵数减少试验确认了因伊维菌素(IVM)和奥芬达唑(OXF)耐药性而被选中的轮虫分离株的耐药性状况,并利用 RT-qPCR 评估了 7 种 ABC 转运体在两种生物情景下的基因表达:抗蠕虫药耐药性选择的影响和药物暴露对基因表达的影响。基因表达结果表明,选择 IVM 抗性会导致 Hco-pgp-9a(1.5 倍)、Hco-pgp-11(3 倍)和 Hco-haf-9 (1.5 倍)显著上调(p < 0.05)。同样,与未选择的 ISE 分离物相比,抗 OXF 选择导致 Hco-pgp-9a(3 倍)、Hco-pgp-11(4 倍)和 Hco-haf-9 (2 倍)显著上调(p < 0.05)。将选定的分离物暴露于抗蠕虫药物不会导致所研究的转运体基因显著上调。我们还观察到,来自不同宿主的寄生虫样本的组内差异很大,这表明动物宿主与受测抗虫药的相互作用也可能在所研究的线虫基因表达中发挥作用。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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