在Haemonchus contortus的抗甲虫药物耐药分离物中,载体基因的表达
Janaelia Ferreira Vasconcelos Rodrigues1, Jessica Maria Leite Dos Santos1, Gracielle Araújo Frota2
1Centro universitário INTA (UNINTA), Programa de Pós-Graduação em Biotecnologia, Sobral, CE, Brazil.
Genetics and molecular biology
|August 19, 2024
概括
在Haemonchus contortus中选择抗甲虫药物耐药性显著提高ATP结合盒 (ABC) 载体的调节,包括P-糖蛋白 (PGP). 药物暴露并没有改变基因表达,这表明宿主-寄生虫相互作用可能会影响载体基因表达.
科学领域:
- 兽医寄生虫学 兽医寄生虫学
- 分子生物学分子生物学
- 药物耐药性机制 药物耐药性机制
背景情况:
- ATP结合盒 (ABC) 载体,特别是P-糖蛋白 (PGP),对于介导寄生性线虫的耐药性至关重要.
- 畜牧业的重要胃肠道线虫Haemonchus contortus对广泛使用的杀虫剂呈现出越来越大的耐药性.
- 了解H.contortus抗甲虫药物耐药性的分子基础对于可持续的寄生虫控制至关重要.
研究的目的:
- 为了确认H.contortus分离物中的甲虫耐药性状态.
- 为了研究抗抗伊弗梅克丁 (IVM) 和牛津醇 (OXF) 的选择对七种ABC载体的基因表达的影响.
- 评估直接药物暴露对这些载体基因表达的影响.
主要方法:
- 便卵数减少试验 (FECRT) 用于确定耐药性状态.
- 定量实时PCR (RT-qPCR) 用于测量七个ABC载体的基因表达水平.
- 选择和未选择的H. contortus分离物之间的基因表达的比较,以及暴露于药物和未暴露的分离物之间的比较.
主要成果:
- 对IVM耐药性的选择显著提高了Hco-pgp-9a (1.5倍),Hco-pgp-11 (3倍) 和Hco-haf-9 (1.5倍) 的调节.
- 与未经选择的分离物相比,对OXF耐药性的选择显著提高了Hco-pgp-9a (3倍),Hco-pgp-11 (4倍) 和Hco-haf-9 (2倍).
- 直接暴露于IVM或OXF的选定H.contortus分离物,并没有导致研究的ABC载体基因表达的显著变化.
- 观察到基因表达的显著群内变异,可能与宿主-寄生虫相互作用有关.
结论:
- 在H. contortus中选择对IVM和OXF的耐药性与特定的ABC转运基因的上调相关.
- 在直接接触药物时缺乏显著的基因上调,这表明在急性药物存在之前或独立于急性药物存在时可能建立了耐药性机制.
- 宿主-寄生虫相互作用需要进一步研究,因为它可能是影响线虫载体基因表达和杀虫剂疗效的潜在因素.
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