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Characterization of benzimidazole resistance in Haemonchus contortus: integration of phenotypic, genotypic and proteomic approaches.
Parasitol Res. 2020 Jul 11 [Online ahead of print]PR

Abstract

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.

Authors+Show Affiliations

Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. stanley.monas@gmail.com.Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. limailian@um.edu.my. Centre of Excellence for Research in AIDS (CERIA), University of Malaya, Kuala Lumpur, Malaysia. limailian@um.edu.my.Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.Tropical Infectious Diseases Research and Education Centre (TIDREC), University of Malaya, Kuala Lumpur, Malaysia.Veterinary Research Institute, Jalan Sultan Azlan Shah, Ipoh, Perak, Malaysia.Tropical Infectious Diseases Research and Education Centre (TIDREC), University of Malaya, Kuala Lumpur, Malaysia.Biodiversity Research Center, Academia Sinica, Taipei, Taiwan.Department of Veterinary Services, Ministry of Agriculture and Agro-Based Industry Malaysia, Federal Government Administrative Center, Putrajaya, Malaysia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32651637

Citation

Tan, Tiong Kai, et al. "Characterization of Benzimidazole Resistance in Haemonchus Contortus: Integration of Phenotypic, Genotypic and Proteomic Approaches." Parasitology Research, 2020.
Tan TK, Lim YAL, Chua KH, et al. Characterization of benzimidazole resistance in Haemonchus contortus: integration of phenotypic, genotypic and proteomic approaches. Parasitol Res. 2020.
Tan, T. K., Lim, Y. A. L., Chua, K. H., Chai, H. C., Low, V. L., Bathmanaban, P., Affendi, S., Wang, D., & Panchadcharam, C. (2020). Characterization of benzimidazole resistance in Haemonchus contortus: integration of phenotypic, genotypic and proteomic approaches. Parasitology Research. https://doi.org/10.1007/s00436-020-06790-5
Tan TK, et al. Characterization of Benzimidazole Resistance in Haemonchus Contortus: Integration of Phenotypic, Genotypic and Proteomic Approaches. Parasitol Res. 2020 Jul 11; PubMed PMID: 32651637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of benzimidazole resistance in Haemonchus contortus: integration of phenotypic, genotypic and proteomic approaches. AU - Tan,Tiong Kai, AU - Lim,Yvonne A L, AU - Chua,Kek Heng, AU - Chai,Hwa Chia, AU - Low,Van Lun, AU - Bathmanaban,Premaalatha, AU - Affendi,Sarah, AU - Wang,Daryi, AU - Panchadcharam,Chandrawathani, Y1 - 2020/07/11/ PY - 2019/06/28/received PY - 2020/06/28/accepted PY - 2020/7/12/entrez KW - 2D-DIGE KW - Benzimidazole KW - F200Y KW - FECRT JF - Parasitology research JO - Parasitol. Res. N2 - 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. SN - 1432-1955 UR - https://www.unboundmedicine.com/medline/citation/32651637/Characterization_of_benzimidazole_resistance_in_Haemonchus_contortus:_integration_of_phenotypic,_genotypic_and_proteomic_approaches L2 - https://dx.doi.org/10.1007/s00436-020-06790-5 DB - PRIME DP - Unbound Medicine ER -
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