Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Centre of Excellence for Research in AIDS (CERIA), University of Malaya, Kuala Lumpur, Malaysia.
Parasitol Res. 2020 Sep;119(9):2851-2862. doi: 10.1007/s00436-020-06790-5. Epub 2020 Jul 11.
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.
捻转血矛线虫田间株具有长期的抗驱虫药性。为了理解这一现象，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株中对苯并咪唑类药物的抗性特征进行了描述。粪便卵计数减少试验（FECRT）表明，在研究的菌株中，苯并咪唑类药物的抗性处于关键水平。主要的抗性机制归因于 1 型β-微管蛋白基因中的 F200Y 突变，这是通过 AS-PCR 和直接测序揭示的。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。这些研究说明了抗氧化剂（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）酶的上调以及谷胱甘肽 S-转移酶、苹果酸脱氢酶和其他结构和细胞骨架蛋白（即肌动蛋白、肌钙蛋白 T）的下调。本研究的结果对于更新抗寄生虫药物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的见解至关重要。
