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

Tan, Tiong Kai and Lim, Yvonne A. L. and Chua, Kek Heng and Chai, Hwa Chia and Low, Van Lun and Bathmanaban, Premaalatha and Affendi, Sarah and Wang, Daryi and Panchadcharam, Chandrawathani (2020) Characterization of benzimidazole resistance in Haemonchus contortus: Integration of phenotypic, genotypic and proteomic approaches. Parasitology Research, 119 (9). pp. 2851-2862. ISSN 09320113, DOI https://doi.org/10.1007/s00436-020-06790-5.

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Abstract

The field strain ofHaemonchus contortushas 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 beta-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.

Item Type: Article
Funders: Universiti Malaya [Grant No: H-20001-00-E000061, PV024/2011B]
Uncontrolled Keywords: Benzimidazole; FECRT; F200Y; 2D-DIGE
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Medicine
Centre of Excellence for Research in AIDS (CERiA)
Deputy Vice Chancellor (Research & Innovation) Office > Tropical Infectious Diseases Research and Education Centre
Depositing User: Ms Zaharah Ramly
Date Deposited: 29 Oct 2024 08:24
Last Modified: 29 Oct 2024 08:24
URI: http://eprints.um.edu.my/id/eprint/36551

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