ArticleProceedings of the National Academy of Sciences of the United States of America2010
Discovery of a highly synergistic anthelmintic combination that shows mutual hypersusceptibility.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 79 citations in OpenAlex.
- Resistance to Cry14A family Bacillus thuringiensis crystal proteins in Caenornabditis elegans operates via the nhr-31 transcription factor and vacuolar-type ATPase pathway.PLoS pathogens · 2024Article
- The nematode (Ascaris suum) intestine is a location of synergistic anthelmintic effects of Cry5B and levamisole.PLoS pathogens · 2024Article
- Article
- Abundance, distribution, and expression of nematicidal crystal protein genes in Bacillus thuringiensis strains from diverse habitats.International microbiology : the official journal of the Spanish Society for Microbiology · 2023Article
- Variation in anthelmintic responses are driven by genetic differences among diverse C. elegans wild strains.PLoS pathogens · 2023Article
- Diethylcarbamazine, TRP channels and CaScientific reports · 2022Article
- Article
- An inactivated bacterium (paraprobiotic) expressingOne health (Amsterdam, Netherlands) · 2021Article
- Recombinant Paraprobiotics as a New Paradigm for Treating Gastrointestinal Nematode Parasites of Humans.Antimicrobial agents and chemotherapy · 2021Article
- Pharmacometric Analysis of Tribendimidine Monotherapy and Combination Therapies To Achieve High Cure Rates in Patients with Hookworm Infections.Antimicrobial agents and chemotherapy · 2021Article
- A new paraprobiotic-based treatment for control of Haemonchus contortus in sheep.International journal for parasitology. Drugs and drug resistance · 2020Article
- Cholinergic receptors on intestine cells of Ascaris suum and activation of nAChRs by levamisole.International journal for parasitology. Drugs and drug resistance · 2020Article
- Plant-Based Natural Products for the Discovery and Development of Novel Anthelmintics against Nematodes.Biomolecules · 2020Review
- Harnessing the gut microbiome in the fight against anthelminthic drug resistance.Current opinion in microbiology · 2020Review
- Targeting tRNA-synthetase interactions towards novel therapeutic discovery against eukaryotic pathogens.PLoS neglected tropical diseases · 2020Article
- Article
- Article
- Bacillus thuringiensis Cry5B protein as a new pan-hookworm cure.International journal for parasitology. Drugs and drug resistance · 2018Article
- Whole-Genome Analysis of Bacillus thuringiensis Revealing Partial Genes as a Source of Novel Cry Toxins.Applied and environmental microbiology · 2018Article
- In vivo and in vitro studies of Cry5B and nicotinic acetylcholine receptor agonist anthelmintics reveal a powerful and unique combination therapy against intestinal nematode parasites.PLoS neglected tropical diseases · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The soil-transmitted helminths or nematodes (hookworms, whipworms, and Ascaris) are roundworms that infect more than 1 billion of the poorest peoples and are leading causes of morbidity worldwide. Few anthelmintics are available for treatment, and only one is commonly used in mass drug administrations. New anthelmintics are urgently needed, and crystal (Cry) proteins made by Bacillus thuringiensis are promising new candidates. Combination drug therapies are considered the ideal treatment for infectious diseases. Surprisingly, little work has been done to define the characteristics of anthelmintic combinations. Here, by means of quantitative assays with wild-type and mutants of the roundworm Caenorhabditis elegans, we establish a paradigm for studying anthelmintic combinations using Cry proteins and nicotinic acetylcholine receptor (nAChR) agonists, e.g., tribendimidine and levamisole. We find that nAChR agonists and Cry proteins, like Cry5B and Cry21A, mutually display what is known in the HIV field as hypersusceptibility--when the nematodes become resistant to either class, they become hypersensitive to the other class. Furthermore, we find that when Cry5B and nAChR agonists are combined, their activities are strongly synergistic, producing combination index values as good or better than seen with antitumor, anti-HIV, and insecticide combinations. Our study provides a powerful means by which anthelmintic combination therapies can be examined and demonstrate that the combination of nAChR agonists and Cry proteins has excellent properties and is predicted to give improved cure rates while being recalcitrant to the development of parasite resistance.
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Registered trials
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