Component
Beta-tubulin carrying phenylalanine at position 200
Beta-tubulin carrying phenylalanine at position 200. Species, exposure and limitations are retained in each linked claim.
2 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
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.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
What acts on it
Albendazole-resistant Giardia lines showed major chromosome rearrangements and differences in the cytoskeleton, particularly the median body, implicating the cytoskeleton in the mechanism of resistance, but sequence data spanning the region encoding phenylalanine at position 200 demonstrated that the beta-tubulin gene did not carry a mutation at that codon, suggesting that phenylalanine at position 200 is not necessary for benzimidazole resistance.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/mebendazole-research/9158790.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1e25da8738886a9f416bb8411755eca925e232495786f938ef8f9afac40de30", "start_char": 0, "end_char": 1295, "text_sha256": "b1e25da8738886a9f416bb8411755eca925e232495786f938ef8f9afac40de30"}
- experimental_model
- Albendazole resistance induced in three Giardia cultures by stepwise drug exposure, with beta-tubulin sequencing
- exposure
- Growth in successively increasing albendazole, with immunofluorescence and PCR across codon 200
- limitations
- A counterexample obtained with albendazole rather than mebendazole, in a protozoan rather than a nematode. It is recorded because it tests the codon-200 rule directly and the rule fails.
- 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
- Giardia
- plain_language
- Resistant parasites that never touched the famous mutation, so it cannot be the only route.
- primary_references
- [mbz-p9158790] Albendazole resistance in Giardia is correlated with cytoskeletal changes but not with a mutation at amino acid 200 in beta-tubulin. (1996). https://pubmed.ncbi.nlm.nih.gov/9158790/ DOI: 10.1089/mdr.1996.2.303
- tissue_or_cell_type
- Cytoskeleton and beta-tubulin gene
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Albendazole resistance induced in three Giardia cultures by stepwise drug exposure, with beta-tubulin sequencing · source_derived_draft · unverified_draft
### mbz-resistance-without-codon-200 Albendazole-resistant Giardia lines showed major chromosome rearrangements and differences in the cytoskeleton, particularly the median body, implicating the cytoskeleton in the mechanism of resistance, but sequence data spanning the region encoding phenylalanine at position 200 demonstrated that the beta-tubulin gene did not carry a mutation at that codon, suggesting that phenylalanine at position 200 is not necessary for benzimidazole resistance. 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 parasites that never touched the famous mutation, so it cannot be the only route. organism: Giardia tissue_or_cell_type: Cytoskeleton and beta-tubulin gene experimental_model: Albendazole resistance induced in three Giardia cultures by stepwise drug exposure, with beta-tubulin sequencing limitations: A counterexample obtained with albendazole rather than mebendazole, in a protozoan rather than a nematode. It is recorded because it tests the codon-200 rule directly and the rule fails. exposure: Growth in successively increasing albendazole, with immunofluorescence and PCR across codon 200 evidence_span: {"source_cache": "artifacts/mebendazole-research/9158790.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1e25da8738886a9f416bb8411755eca925e232495786f938ef8f9afac40de30", "start_char": 0, "end_char": 1295, "text_sha256": "b1e25da8738886a9f416bb8411755eca925e232495786f938ef8f9afac40de30"} [mbz-p9158790] Albendazole resistance in Giardia is correlated with cytoskeletal changes but not with a mutation at amino acid 200 in beta-tubulin. (1996). https://pubmed.ncbi.nlm.nih.gov/9158790/ DOI: 10.1089/mdr.1996.2.303
Complete structured claim and evidence
Where it participates (unsigned role)
All Haemonchus contortus tub-1 constructs encoding phenylalanine at position 200 conferred susceptibility to thiabendazole in benzimidazole-resistant Caenorhabditis elegans ben-1 mutants, whereas constructs carrying tyrosine at position 200 did not alter the resistant phenotype, leading to the conclusion that the single phenylalanine to tyrosine mutation at position 200 in beta-tubulin isotype 1 is the cause of benzimidazole resistance in Haemonchus contortus.
Experimental context and source evidence
- availability_state
- machinery_impairment Imported condition classification; unverified.
- evidence_span
- {"source_cache": "artifacts/mebendazole-research/7877171.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "091ba3ac445b68112bac29dec56d0d1a48e0d258714ebdbe090b5e7728e6ceaa", "start_char": 0, "end_char": 1532, "text_sha256": "091ba3ac445b68112bac29dec56d0d1a48e0d258714ebdbe090b5e7728e6ceaa"}
- experimental_model
- Heterologous expression of Haemonchus contortus beta-tubulin alleles in Caenorhabditis elegans ben-1 mutants
- exposure
- Parasite benzimidazole-sensitive and resistant alleles and in vitro mutagenised constructs, assayed with benomyl and thiabendazole
- limitations
- A functional test rather than an association: the alleles were put into a resistant host and the phenotype followed the codon. The assay drugs were benomyl and thiabendazole rather than mebendazole.
- 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
- Swapping one amino acid back made resistant worms susceptible again, which makes it the cause and not a coincidence.
- primary_references
- [mbz-p7877171] Beta-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. (1995). https://pubmed.ncbi.nlm.nih.gov/7877171/ DOI: 10.1006/jmbi.1994.0102
- tissue_or_cell_type
- Beta-tubulin isotype 1
- trigger_kind
- machinery_impairment Imported condition classification; unverified.
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous expression of Haemonchus contortus beta-tubulin alleles in Caenorhabditis elegans ben-1 mutants · source_derived_draft · unverified_draft
### mbz-phe200-causes-resistance All Haemonchus contortus tub-1 constructs encoding phenylalanine at position 200 conferred susceptibility to thiabendazole in benzimidazole-resistant Caenorhabditis elegans ben-1 mutants, whereas constructs carrying tyrosine at position 200 did not alter the resistant phenotype, leading to the conclusion that the single phenylalanine to tyrosine mutation at position 200 in beta-tubulin isotype 1 is the cause of benzimidazole resistance in Haemonchus contortus. Condition category: machinery_impairment 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: Swapping one amino acid back made resistant worms susceptible again, which makes it the cause and not a coincidence. organism: Nematode tissue_or_cell_type: Beta-tubulin isotype 1 experimental_model: Heterologous expression of Haemonchus contortus beta-tubulin alleles in Caenorhabditis elegans ben-1 mutants limitations: A functional test rather than an association: the alleles were put into a resistant host and the phenotype followed the codon. The assay drugs were benomyl and thiabendazole rather than mebendazole. exposure: Parasite benzimidazole-sensitive and resistant alleles and in vitro mutagenised constructs, assayed with benomyl and thiabendazole evidence_span: {"source_cache": "artifacts/mebendazole-research/7877171.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "091ba3ac445b68112bac29dec56d0d1a48e0d258714ebdbe090b5e7728e6ceaa", "start_char": 0, "end_char": 1532, "text_sha256": "091ba3ac445b68112bac29dec56d0d1a48e0d258714ebdbe090b5e7728e6ceaa"} [mbz-p7877171] Beta-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. (1995). https://pubmed.ncbi.nlm.nih.gov/7877171/ DOI: 10.1006/jmbi.1994.0102
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
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.