Anthelmintic metabolism in parasitic helminths: proteomic insights.
Abstract: Anthelmintics are the cornerstone of parasitic helminth control. Surprisingly, understanding of the biochemical pathways used by parasitic helminths to detoxify anthelmintics is fragmented, despite the increasing global threat of anthelmintic resistance within the ruminant and equine industries. Reductionist biochemistry has likely over-estimated the enzymatic role of glutathione transferases in anthelmintic metabolism and neglected the potential role of the cytochrome P-450 superfamily (CYPs). Proteomic technologies offers the opportunity to support genomics, reverse genetics and pharmacokinetics, and provide an integrated insight into both the cellular mechanisms underpinning response to anthelmintics and also the identification of biomarker panels for monitoring the development of anthelmintic resistance. To date, there have been limited attempts to include proteomics in anthelmintic metabolism studies. Optimisations of membrane, post-translational modification and interaction proteomic technologies in helminths are needed to especially study Phase I CYPs and Phase III ABC transporter pumps for anthelmintics and their metabolites.
Publication Date: 2012-07-10 PubMed ID: 22776506DOI: 10.1017/S003118201200087XGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Review
Summary
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This research article looks into the mechanisms used by parasitic worms to metabolize anthelmintic drugs. It highlights the importance of understanding these biochemical pathways due to the growing threat of anthelmintic resistance, and suggests use of proteomic technologies for a more integrated study.
Understanding Anthelmintic Metabolism
- The research emphasizes on the importance of anthelmintics in controlling parasitic worms. However, it notes that the knowledge of how these worms metabolize the anthelmintics is quite fragmented.
- There is also a growing global threat of resistance to these drugs within the ruminant and equine industries. Therefore, understanding the mechanisms employed by parasitic helminths to metabolize these drugs is crucial.
- The study claims that reductionist biochemistry, a method that often simplifies complex biochemical interactions for easy study, has possibly overestimated the role of glutathione transferases, enzymes involved in detoxification, in anthelmintic metabolism while ignoring the possible role of the cytochrome P-450 superfamily (CYPs).
Role of Proteomic Technologies
- Proteomic technologies can help fully understand the cellular mechanisms behind the response to anthelmintics. Besides, it would also allow identifying biomarker panels that monitor the development of anthelmintic resistance.
- This can support genomics, reverse genetics and pharmacokinetics studies, providing a multifaceted view of anthelmintic metabolism.
- Unfortunately, proteomics has been underutilized in studying anthelmintic metabolism. This paper suggests its optimization in helminths to study Phase I CYPs, enzymes responsible for metabolizing drugs, and Phase III ATP-binding cassette (ABC) transporter pumps, proteins indicating drug resistance.
Cite This Article
APA
Brophy PM, MacKintosh N, Morphew RM.
(2012).
Anthelmintic metabolism in parasitic helminths: proteomic insights.
Parasitology, 139(9), 1205-1217.
https://doi.org/10.1017/S003118201200087X Publication
Researcher Affiliations
- Parasitology Group, Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, Ceredigion, Wales SY23 3FG, UK. pmb@aber.ac.uk
MeSH Terms
- ATP-Binding Cassette Transporters / metabolism
- Animals
- Anthelmintics / pharmacology
- Anthelmintics / therapeutic use
- Biological Transport
- Drug Resistance / genetics
- Helminthiasis / drug therapy
- Helminthiasis / parasitology
- Helminths / drug effects
- Helminths / genetics
- Helminths / metabolism
- Protein Processing, Post-Translational
- Proteomics / methods
Grant Funding
- BB/H009256/1 / Biotechnology and Biological Sciences Research Council
- BBH0092561 / Biotechnology and Biological Sciences Research Council
Citations
This article has been cited 13 times.- Allen NR, Huson KM, Prchal L, Robinson MW, Brophy PM, Morphew RM. Detoxome Capacity of the Adult Rumen Fluke Calicophoron daubneyi Extends into Its Secreted Extracellular Vesicles. J Proteome Res 2025 Feb 7;24(2):624-638.
- Vosála O, Krátký J, Matoušková P, Rychlá N, Štěrbová K, Raisová Stuchlíková L, Vokřál I, Skálová L. Biotransformation of anthelmintics in nematodes in relation to drug resistance. Int J Parasitol Drugs Drug Resist 2025 Apr;27:100579.
- Zheng M, Jiang X, Kong X, Guo Y, Zhang W, Di W. Proteomic analysis of Fasciola gigantica excretory and secretory products (FgESPs) co-immunoprecipitated using a time course of infected buffalo sera. Front Microbiol 2022;13:1089394.
- Kamil Jabbar D. Biochemical Evaluation of Antioxidant Enzyme Activities and Lipid Peroxidation Level Associated with Liver Enzymes in Patients with Fascioliasis. Arch Razi Inst 2022 Jun;77(3):1067-1073.
- Stuart RB, Zwaanswijk S, MacKintosh ND, Witikornkul B, Brophy PM, Morphew RM. The soluble glutathione transferase superfamily: role of Mu class in triclabendazole sulphoxide challenge in Fasciola hepatica. Parasitol Res 2021 Mar;120(3):979-991.
- Davis CN, Winters A, Milic I, Devitt A, Cookson A, Brophy PM, Morphew RM. Evidence of sequestration of triclabendazole and associated metabolites by extracellular vesicles of Fasciola hepatica. Sci Rep 2020 Aug 10;10(1):13445.
- Polak I, Łopieńska-Biernat E, Stryiński R, Mateos J, Carrera M. Comparative Proteomics Analysis of Anisakis simplex s.s.-Evaluation of the Response of Invasive Larvae to Ivermectin. Genes (Basel) 2020 Jun 26;11(6).
- Line K, Isupov MN, LaCourse EJ, Cutress DJ, Morphew RM, Brophy PM, Littlechild JA. X-ray structure of Fasciola hepatica Sigma class glutathione transferase 1 reveals a disulfide bond to support stability in gastro-intestinal environment. Sci Rep 2019 Jan 29;9(1):902.
- Pawluk RJ, Stuart R, Garcia de Leaniz C, Cable J, Morphew RM, Brophy PM, Consuegra S. Smell of Infection: A Novel, Noninvasive Method for Detection of Fish Excretory-Secretory Proteins. J Proteome Res 2019 Mar 1;18(3):1371-1379.
- Huson KM, Morphew RM, Allen NR, Hegarty MJ, Worgan HJ, Girdwood SE, Jones EL, Phillips HC, Vickers M, Swain M, Smith D, Kingston-Smith AH, Brophy PM. Polyomic tools for an emerging livestock parasite, the rumen fluke Calicophoron daubneyi; identifying shifts in rumen functionality. Parasit Vectors 2018 Dec 4;11(1):617.
- Stuchlíková LR, Matoušková P, Vokřál I, Lamka J, Szotáková B, Sečkařová A, Dimunová D, Nguyen LT, Várady M, Skálová L. Metabolism of albendazole, ricobendazole and flubendazole in Haemonchus contortus adults: Sex differences, resistance-related differences and the identification of new metabolites. Int J Parasitol Drugs Drug Resist 2018 Apr;8(1):50-58.
- Hansen TV, Nejsum P, Friis C, Olsen A, Thamsborg SM. Trichuris suis and Oesophagostomum dentatum show different sensitivity and accumulation of fenbendazole, albendazole and levamisole in vitro. PLoS Negl Trop Dis 2014 Apr;8(4):e2752.
- Rana AK, Misra-Bhattacharya S. Current drug targets for helminthic diseases. Parasitol Res 2013 May;112(5):1819-31.
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