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Characterization of benzimidazole resistance in Haemonchus contortus: integration of phenotypic, genotypic and proteomic approaches.
Parasitology Research ( IF 1.8 ) Pub Date : 2020-07-11 , DOI: 10.1007/s00436-020-06790-5
Tiong Kai Tan , Yvonne A. L. Lim , Kek Heng Chua , Hwa Chia Chai , Van Lun Low , Premaalatha Bathmanaban , Sarah Affendi , Daryi Wang , Chandrawathani Panchadcharam

The field strain of Haemonchus contortus has a long history of anthelmintic resistance. To understand this phenomenon, the benzimidazole resistance profile was characterized from the Malaysian field-resistant strain by integrating phenotypic, genotypic and proteomic approaches. The faecal egg count reduction test (FECRT) demonstrated that benzimidazole resistance was at a critical level in the studied strain. The primary resistance mechanism was attributed to F200Y mutation in the isotype 1 β-tubulin gene as revealed by AS-PCR and direct sequencing. Furthermore, the protein response of the resistant strain towards benzimidazole (i.e., albendazole) treatment was investigated via two-dimensional difference gel electrophoresis (2D-DIGE) and tandem liquid chromatography-mass spectrometry (LC-MS/MS). These investigations illustrated an up-regulation of antioxidant (i.e., ATP-binding region and heat-shock protein 90, superoxide dismutase) and metabolic (i.e., glutamate dehydrogenase) enzymes and down-regulation of glutathione S-transferase, malate dehydrogenase, and other structural and cytoskeletal proteins (i.e., actin, troponin T). Findings from this study are pivotal in updating the current knowledge on anthelmintic resistance and providing new insights into the defence mechanisms of resistant nematodes towards drug treatment.



中文翻译:

捻转血矛线虫对苯并咪唑的抗性特征:表型,基因型和蛋白质组学方法的整合。

捻转血矛线虫的田间应变具有驱虫抗药性的悠久历史。为了理解这种现象,通过整合表型,基因型和蛋白质组学方法,从马来西亚田间抗性菌株中鉴定了苯并咪唑抗性概况。粪便卵数减少测试(FECRT)表明,在研究的菌株中,苯并咪唑耐药性处于临界水平。如AS-PCR和直接测序所揭示的,主要的抗性机制归因于同型1β-微管蛋白基因中的F200Y突变。此外,通过二维差异凝胶电泳(2D-DIGE)和串联液相色谱-质谱(LC-MS / MS)研究了抗性菌株对苯并咪唑(即阿苯达唑)处理的蛋白质反应。这些调查表明抗氧化剂的上调(即 ATP结合区和热休克蛋白90,超氧化物歧化酶)和代谢(即谷氨酸脱氢酶)酶以及谷胱甘肽S-转移酶,苹果酸脱氢酶以及其他结构和细胞骨架蛋白(例如肌动蛋白,肌钙蛋白T)的下调。这项研究的发现对于更新有关驱虫药抗性的现有知识以及为耐药线虫对药物治疗的防御机制提供新见解至关重要。

更新日期:2020-07-13
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