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捻转血矛线虫抗驱虫药分离株中转运蛋白基因的表达

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

作者信息

Rodrigues Janaelia Ferreira Vasconcelos, Santos Jessica Maria Leite Dos, Frota Gracielle Araújo, Vieira Luiz da Silva, Teixeira Marcel, Monteiro Magaly Sales, Monteiro Jomar Patrício

机构信息

Centro universitário INTA (UNINTA), Programa de Pós-Graduação em Biotecnologia, Sobral, CE, Brazil.

Universidade Estadual Vale do Acaraú (UVA), Programa de Pós-Graduação em Zootecnia, Sobral, CE, Brazil.

出版信息

Genet Mol Biol. 2024 Aug 16;47(3):e20230350. doi: 10.1590/1678-4685-GMB-2023-0350. eCollection 2024.

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.

摘要

包括P-糖蛋白(PGP)在内的ATP结合盒(ABC)转运蛋白与多种生物(包括捻转血矛线虫)的耐药性有关。本研究使用粪便虫卵计数减少试验确认了选择伊维菌素(IVM)和奥芬达唑(OXF)耐药的捻转血矛线虫分离株的耐药状态,并针对两种生物学情况使用RT-qPCR评估了7种ABC转运蛋白的基因表达:抗蠕虫药耐药性选择的影响以及药物暴露对基因表达的影响。基因表达结果表明,选择IVM耐药导致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分离株相比,选择OXF耐药导致Hco-pgp-9a(3倍)、Hco-pgp-11(4倍)和Hco-haf-9(2倍)显著上调(p<0.05)。将选择的分离株暴露于驱虫药不会导致所研究的转运蛋白基因显著上调。我们还观察到,来自不同个体宿主的寄生虫样本在组内存在强烈差异,这表明动物宿主与受试驱虫药的相互作用可能也在研究的线虫基因表达中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/911e/11331566/22961d7b2435/1415-4757-GMB-47-03-e20230350-gf1.jpg

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