Characterization of benzimidazole resistance in Haemonchus contortus: integration of phenotypic, genotypic and proteomic approaches

• Published in: Parasitology research (1987) Vol. 119; no. 9; pp. 2851 - 2862
• Main Authors: Tan, Tiong Kai, Lim, Yvonne A. L., Chua, Kek Heng, Chai, Hwa Chia, Low, Van Lun, Bathmanaban, Premaalatha, Affendi, Sarah, Wang, Daryi, Panchadcharam, Chandrawathani
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2020; Springer; Springer Nature B.V
• Subjects: Actin; Albendazole; Anthelmintic agents; Antioxidants; Benzimidazoles; Biomedical and Life Sciences; Biomedicine; Calcium-binding protein; Cytoskeleton; Dehydrogenases; Gel electrophoresis; Glutamate dehydrogenase; Glutathione transferase; Haemonchus contortus; Helminthology - Original Paper; Immunology; Instrument industry; International economic relations; Liquid chromatography; Malate dehydrogenase; Mass spectrometry; Mass spectroscopy; Medical Microbiology; Microbiology; Nematoda; Pest resistance; Protein binding; Superoxide dismutase; Troponin; Troponin T; Tubulin; Tubulins; United States; Malaysia; FECRT; F200Y; 2D-DIGE; Benzimidazole
• ISSN: 0932-0113; 1432-1955
• DOI: 10.1007/s00436-020-06790-5

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.