Fumarate reductase of Haemonchus contortus: molecular mechanisms & dependencies

How nutrients influence it

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Human evidence only

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

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What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

Fumarate reductase activity in a thiabendazole-resistant Haemonchus contortus strain was significantly lower than in a susceptible strain, but activity in a mebendazole-resistant strain did not differ from the susceptible strain even though it was cross-resistant to thiabendazole, and on reassessment two American strains resistant to thiabendazole and to cambendazole had activities indistinguishable from corresponding susceptible strains, so that benzimidazole resistance cannot be generally correlated with diminished fumarate reductase activity although it may be a contributory factor in the specific Australian thiabendazole-resistant strains.
Fumarate reductase of Haemonchus contortus → Resistance to benzimidazole anthelmintics source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/mebendazole-research/6877276.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59837d0bc8f0d0c120dd9d647dcd86cd046545768ec6ab198e2262d381aafbf7", "start_char": 0, "end_char": 1052, "text_sha256": "59837d0bc8f0d0c120dd9d647dcd86cd046545768ec6ab198e2262d381aafbf7"}
experimental_model
Fumarate reductase activity compared across benzimidazole-susceptible and resistant Haemonchus contortus strains, with reassessment of published reports
exposure
Thiabendazole-resistant, mebendazole-resistant and susceptible strains
limitations
A proposed resistance mechanism tested across strains and largely rejected. The reassessment of other laboratories’ published values is the useful part.
nutrient_topic
Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. · Mebendazole
organism
Nematode
plain_language
A once-popular explanation for resistance, checked across strains and found not to hold.
primary_references
[mbz-p6877276] Observations on the fumarate reductase system in Haemonchus contortus and their relevance to anthelmintic resistance and to strain variations of energy metabolism. (1983). https://pubmed.ncbi.nlm.nih.gov/6877276/ DOI: 10.1016/0166-6851(83)90011-7
tissue_or_cell_type
Mitochondrial electron transport
Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 329–340
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fumarate reductase activity compared across benzimidazole-susceptible and resistant Haemonchus contortus strains, with reassessment of published reports · source_derived_draft · unverified_draft
### mbz-fumarate-reductase-retired Fumarate reductase activity in a thiabendazole-resistant Haemonchus contortus strain was significantly lower than in a susceptible strain, but activity in a mebendazole-resistant strain did not differ from the susceptible strain even though it was cross-resistant to thiabendazole, and on reassessment two American strains resistant to thiabendazole and to cambendazole had activities indistinguishable from corresponding susceptible strains, so that benzimidazole resistance cannot be generally correlated with diminished fumarate reductase activity although it may be a contributory factor in the specific Australian thiabendazole-resistant strains. Condition category: normal nutrient_topic: Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. plain_language: A once-popular explanation for resistance, checked across strains and found not to hold. organism: Nematode tissue_or_cell_type: Mitochondrial electron transport experimental_model: Fumarate reductase activity compared across benzimidazole-susceptible and resistant Haemonchus contortus strains, with reassessment of published reports limitations: A proposed resistance mechanism tested across strains and largely rejected. The reassessment of other laboratories’ published values is the useful part. exposure: Thiabendazole-resistant, mebendazole-resistant and susceptible strains evidence_span: {"source_cache": "artifacts/mebendazole-research/6877276.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59837d0bc8f0d0c120dd9d647dcd86cd046545768ec6ab198e2262d381aafbf7", "start_char": 0, "end_char": 1052, "text_sha256": "59837d0bc8f0d0c120dd9d647dcd86cd046545768ec6ab198e2262d381aafbf7"} [mbz-p6877276] Observations on the fumarate reductase system in Haemonchus contortus and their relevance to anthelmintic resistance and to strain variations of energy metabolism. (1983). https://pubmed.ncbi.nlm.nih.gov/6877276/ DOI: 10.1016/0166-6851(83)90011-7
Complete structured claim and evidence

Where it participates (unsigned role)

Steady-state pool sizes of glucose and metabolic intermediates including adenine nucleotides and end products revealed no differences between adult Haemonchus contortus resistant or susceptible to benzimidazoles, all three strains had similar levels of total lipid, protein and free amino acid and produced a similar sum total of end products, and although the mebendazole-resistant strain showed a diversion of carbon flow to the ethanol-producing pathway and greater cyanide-sensitive aerobic carbon dioxide output, the extent to which these metabolic differences may be related to benzimidazole resistance is not readily apparent.
Carbohydrate and energy metabolism of the parasite → Resistance to benzimidazole anthelmintics source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/mebendazole-research/6427605.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4834a68834e7916938d61b08f8dc38fb00085c0b43761372c8ef883da0d8cbf8", "start_char": 0, "end_char": 1809, "text_sha256": "4834a68834e7916938d61b08f8dc38fb00085c0b43761372c8ef883da0d8cbf8"}
experimental_model
Biochemical comparison of susceptible, mebendazole-resistant and thiabendazole-resistant Haemonchus contortus in vitro
exposure
Steady-state metabolite pools, end products and labelled carbon dioxide over 30 to 60 minute and 18 hour incubations
limitations
A broad metabolic survey across matched resistant and susceptible strains. Its own authors state the relationship to resistance is not apparent.
nutrient_topic
Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. · Mebendazole
organism
Nematode
plain_language
Resistant and susceptible worms handle sugar much the same, so metabolism is not where resistance lives.
primary_references
[mbz-p6427605] Energy metabolism of adult Haemonchus contortus in vitro: a comparison of benzimidazole-susceptible and -resistant strains. (1984). https://pubmed.ncbi.nlm.nih.gov/6427605/ DOI: 10.1016/0166-6851(84)90031-8
tissue_or_cell_type
Whole adult worms
Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 342–353
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical comparison of susceptible, mebendazole-resistant and thiabendazole-resistant Haemonchus contortus in vitro · source_derived_draft · unverified_draft
### mbz-metabolism-does-not-explain-resistance Steady-state pool sizes of glucose and metabolic intermediates including adenine nucleotides and end products revealed no differences between adult Haemonchus contortus resistant or susceptible to benzimidazoles, all three strains had similar levels of total lipid, protein and free amino acid and produced a similar sum total of end products, and although the mebendazole-resistant strain showed a diversion of carbon flow to the ethanol-producing pathway and greater cyanide-sensitive aerobic carbon dioxide output, the extent to which these metabolic differences may be related to benzimidazole resistance is not readily apparent. Condition category: normal nutrient_topic: Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. plain_language: Resistant and susceptible worms handle sugar much the same, so metabolism is not where resistance lives. organism: Nematode tissue_or_cell_type: Whole adult worms experimental_model: Biochemical comparison of susceptible, mebendazole-resistant and thiabendazole-resistant Haemonchus contortus in vitro limitations: A broad metabolic survey across matched resistant and susceptible strains. Its own authors state the relationship to resistance is not apparent. exposure: Steady-state metabolite pools, end products and labelled carbon dioxide over 30 to 60 minute and 18 hour incubations evidence_span: {"source_cache": "artifacts/mebendazole-research/6427605.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4834a68834e7916938d61b08f8dc38fb00085c0b43761372c8ef883da0d8cbf8", "start_char": 0, "end_char": 1809, "text_sha256": "4834a68834e7916938d61b08f8dc38fb00085c0b43761372c8ef883da0d8cbf8"} [mbz-p6427605] Energy metabolism of adult Haemonchus contortus in vitro: a comparison of benzimidazole-susceptible and -resistant strains. (1984). https://pubmed.ncbi.nlm.nih.gov/6427605/ DOI: 10.1016/0166-6851(84)90031-8
Complete structured claim and evidence

The events it takes part in

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Situations it appears in

Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.

In the sources

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Open hypotheses

Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.

This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

Fumarate reductase of Haemonchus contortus