Article
Parasitology
Elise Courtot, Morgane Miclon, Barbara Reaves, Adrian J. Wolstenholme, Cedric Neveu
Summary: Levamisole is a broad-spectrum anthelmintic used to control parasitic nematodes impacting livestock, but its efficacy is compromised by drug-resistant parasites. This study investigates truncated cholinergic receptor sub-units as potential levamisole resistance markers in nematodes. The researchers used Xenopus oocyte and Caenorhabditis elegans as expression systems to functionally investigate these markers. They found that truncated UNC-63 induces a reduction in levamisole susceptibility, providing the first functional validation for this molecular marker.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2023)
Article
Microbiology
Amanda C. Shaver, Janneke Wit, Clayton Dilks, Timothy Crombie, Hanchen Li, Raffi Aroian, Erik Andersen
Summary: Treatment of parasitic nematode infections in humans and livestock is becoming a challenge due to the increasing anthelmintic resistance. However, the use of Caenorhabditis elegans as a model organism has provided insights into the molecular targets of anthelmintic drugs. By studying genetically diverse strains of C. elegans, researchers were able to identify variations in anthelmintic responses and quantify the contribution of genetics to resistance. This study highlights the importance of using genetically diverse models to understand anthelmintic resistance.
Article
Multidisciplinary Sciences
Daniela Bedenice, Jessica Resnick-Sousa, Lauren Bookbinder, Victoria Trautwein, Hannah N. Creasey, Giovanni Widmer
Summary: This study examined the correlation between nematode worm burden and intestinal microbiota composition in adult alpacas. Fecal samples were collected from 102 healthy alpacas at three different time points. The results showed high temporal stability in the fecal microbiota of healthy alpacas. The intensity of nematode infection was only significantly correlated with microbiota composition 14 days after treatment. Alpaca age was found to be the only consistent predictor of microbiota taxonomic composition.
Article
Multidisciplinary Sciences
Jeba R. J. Jesudoss Chelladurai, Katy A. Martin, Pam Vardaxis, Craig Reinemeyer, Paramasivan Vijayapalani, Alan P. Robertson, Matthew T. Brewer
Summary: In this study, the researchers investigated the role of permeability glycoproteins (P-gps) in Toxocara canis drug tolerance. They found that T. canis has 13 annotated P-gp genes, with at least 10 expressed in adults and hatched larvae, and at least 8 expressed in somatic larvae. However, treatment with macrocyclic lactones did not significantly increase P-gp expression. Further studies are needed to understand the contribution of P-gps to macrocyclic lactone tolerance in T. canis.
SCIENTIFIC REPORTS
(2023)
Article
Veterinary Sciences
Michal Babjak, Alzbeta Konigova, Michaela Komaromyova, Tetiana Kuzmina, Pawel Nosal, Marian Varady
Summary: This study was conducted to investigate the resistance of Haemonchus contortus to albendazole and ivermectin. The results showed reduced efficacy of albendazole and ivermectin, while levamisole was found to be an efficient anthelmintic treatment.
JOURNAL OF VETERINARY RESEARCH
(2023)
Article
Parasitology
Paulius Baltrusis, Claude L. Charvet, Peter Halvarsson, Sofia Mikko, Johan Hoglund
Summary: The nematode Haemonchus contortus is a common and pathogenic parasite in small ruminants, and detecting resistance to levamisole in this parasite is challenging. A new droplet digital PCR assay was developed to detect a specific gene deletion associated with levamisole resistance in H. contortus.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2021)
Article
Veterinary Sciences
Paula Suarez-Henriques, Camila de Miranda e Silva Chaves, Ricardo Cardoso-Leite, Danielle G. Gomes-Caldas, Luciana Morita-Katiki, Siu Mui Tsai, Helder Louvandini
Summary: Protein supplementation in infected ewe lambs led to the up-regulation of genes and biological processes linked to meiotic activation in pre-ovulatory follicles and primordial follicle activation. This supplementation allowed infected animals to express genes related to a more mature ovarian follicle stage compared to their non-supplemented half-sisters.
BMC VETERINARY RESEARCH
(2021)
Article
Parasitology
Marco A. Munoz-Guzman, A. Sanchez-Paredes, C. Cuenca-Verde, M. E. Lopez-Arellano, F. Alba-Hurtado
Summary: ThLVC treatment can reduce the egg count after H. contortus infection in lambs and modulate the immune response in the abomasal mucosa and lymph nodes. Lambs infected before receiving ThLVC showed higher levels of cytokine expression.
VETERINARY PARASITOLOGY
(2021)
Article
Entomology
Zhi-Min Wang, Sha Li, Cheng-Cheng Shi, Lin-Jie Xie, Kai-Yun Fu, Wei-Hua Jiang
Summary: This study analyzed the molecular interactions between Ld alpha 1 and Ld alpha 8 subunits of L. decemlineata nAChRs and neonicotinoids, and found that Ld alpha 1 and Ld alpha 8 play an important role in the sensitivity to neonicotinoids.
Article
Cell Biology
Stephen R. Doyle, Roz Laing, David Bartley, Alison Morrison, Nancy Holroyd, Kirsty Maitland, Alistair Antonopoulos, Umer Chaudhry, Ilona Flis, Sue Howell, Jennifer McIntyre, John S. Gilleard, Andy Tait, Barbara Mable, Ray Kaplan, Neil Sargison, Collette Britton, Matthew Berriman, Eileen Devaney, James A. Cotton
Summary: Understanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is crucial for improving parasite control. By using an in vivo genetic cross, this study successfully mapped resistance loci for three major classes of anthelmintics and identified new alleles for resistance. The study also implicated a transcription factor in ivermectin resistance and demonstrated the feasibility of high-resolution forward genetics in parasitic nematodes.
Article
Microbiology
David Emanuel Reyes-Guerrero, Veronica Jimenez-Jacinto, Rogelio Alejandro Alonso-Morales, Miguel Angel Alonso-Diaz, Jocelyn Maza-Lopez, Rene Camas-Pereyra, Agustin Olmedo-Juarez, Rosa Isabel Higuera-Piedrahita, Maria Eugenia Lopez-Arellano
Summary: In this study, the transcriptome of Hc was assembled and annotated to investigate the differential gene expression between two Mexican Hc strains with different anthelmintic resistance statuses. The study identified differentially expressed genes and enriched gene ontology terms related to anthelmintic resistance and nematode biology.
Article
Veterinary Sciences
Karolina Sterbova, Nikola Rychla, Petra Matouskova, Lenka Skalova, Lucie Raisova Stuchlikova
Summary: A study characterized the SDR superfamily in the parasitic nematode H. contortus and identified 46 SDR genes, some of which are related to drug resistance. It was found that SDR1, SDR3, SDR5, SDR6, SDR14, and SDR18 genes were highly expressed in all developmental stages of H. contortus, but with significant differences in expression levels between stages.
VETERINARY RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Eleanor L. Mitchell, Franco Viscarra, Isabel Bermudez, Joseph Hawkins, Jim A. Goodchild, Andrew K. Jones
Summary: This study presents the functional expression of the alpha 5 nAChR subunit from honey bees in a heterologous system, revealing its low sensitivity to acetylcholine and the efficacy of serotonin as an agonist. Molecular modelling suggests that residues in the binding site may play a role in the receptor's selectivity towards serotonin. This finding may provide potential targets for the development of novel insecticides.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2022)
Article
Microbiology
Roz Laing, Stephen R. Doyle, Jennifer McIntyre, Kirsty Maitland, Alison Morrison, David J. Bartley, Ray Kaplan, Umer Chaudhry, Neil Sargison, Andy Tait, James A. Cotton, Collette Britton, Eileen Devaney
Summary: Through crossbreeding and gene expression analysis, we have identified certain genes associated with ivermectin resistance and proposed a novel mechanism that allows resistant worms to survive treatment. This is crucial for understanding ivermectin resistance and response to treatment in parasitic helminths.
Article
Engineering, Environmental
Stephen Short, Alex Robinson, Elma Lahive, Amaia Green Etxabe, Szabolcs Hernadi, M. Gloria Pereira, Peter Kille, David J. Spurgeon
Summary: Neonicotinoids, widely used in 120 countries, require accurate prediction of nontarget species sensitivity. Combining toxicology with toxicogenomics can improve predictions and identify susceptible species. Variations in AChBP expression can explain differential species sensitivity to neonicotinoids.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Review
Parasitology
Richard J. Martin, Alan P. Robertson, Shivani Choudhary
Summary: Ivermectin has diverse effects, including anthelmintic and insecticidal actions as well as antiviral, antimalarial, antimetabolic, and anticancer effects. However, caution is needed when considering its repositioning for the treatment of other diseases, particularly Covid-19, due to the potential risks associated with the high concentrations used in tissue-culture experiments.
TRENDS IN PARASITOLOGY
(2021)
Article
Microbiology
Tina V. A. Hansen, Susanna Cirera, Cedric Neveu, Elise Courtot, Claude L. Charvet, Kirstine Calloe, Dan A. Klaerke, Richard J. Martin
Summary: The study found that the anthelmintic oxantel has high efficacy against the whipworm Trichuris, but its molecular targets are still unknown. By using the pig whipworm as a model, a novel ACR-16-like subunit was identified, shedding light on the sensitivity of whipworms to oxantel. This finding provides new insight into the mechanisms of action of anthelmintic compounds against parasitic nematodes and the potential for future drug development.
Article
Microbiology
Nicolas Lamassiaude, Berthine Toubate, Cedric Neveu, Pierre Charnet, Catherine Dupuy, Francoise Debierre-Grockiego, Isabelle Dimier-Poisson, Claude L. Charvet
Summary: The control of infestation by cosmopolitan lice is increasingly difficult due to resistance to traditional pediculicides. This study investigated the efficacy of ivermectin and lotilaner on killing human lice, revealing their molecular targets and mode of action. Results show that lotilaner was more effective than ivermectin in killing adult lice, providing new insights into potential alternative treatments for human lice infestation.
Article
Chemistry, Medicinal
Alexander P. Gerhard, Juergen Kruecken, Cedric Neveu, Claude L. Charvet, Abdallah Harmache, Georg von Samson-Himmelstjerna
Summary: The active drug ingestion by nematodes has been identified as a crucial factor affecting susceptibility, while P-glycoprotein efflux pumps play a role in tissue-specific resistance mechanisms.
Article
Parasitology
Paulius Baltrusis, Claude L. Charvet, Peter Halvarsson, Sofia Mikko, Johan Hoglund
Summary: The nematode Haemonchus contortus is a common and pathogenic parasite in small ruminants, and detecting resistance to levamisole in this parasite is challenging. A new droplet digital PCR assay was developed to detect a specific gene deletion associated with levamisole resistance in H. contortus.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2021)
Article
Pharmacology & Pharmacy
Nicolas Lamassiaude, Elise Courtot, Angelique Corset, Claude L. Charvet, Cedric Neveu
Summary: This study identified and characterized highly conserved GluCl subunits from different nematode species, revealing the pivotal role of GLC-2 subunit in the composition of heteromeric GluCls and discovering a novel GluCl subtype combining GLC-2/GLC-3 subunits. The findings provide new insights into GluCl diversity and potential drug targets for the development of next generation anthelmintic compounds.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tina V. A. Hansen, Heinz Sager, Celine E. Toutain, Elise Courtot, Cedric Neveu, Claude L. Charvet
Summary: This study investigates the pharmacological characteristics of the DEG-3/DES-2 channel in C. elegans. The results show that the channel is more sensitive to betaine than ACh and choline, but less sensitive to monepantel and monepantel sulfone. These findings provide important insights into the function of the DEG-3/DES-2 channel in C. elegans.
Article
Parasitology
Shivani Choudhary, Sudhanva S. Kashyap, Richard J. Martin, Alan P. Robertson
Summary: This article summarizes the recent advances in nematode ion channel pharmacology, including the updates on different channel types and their pharmacological properties. By comparing the differences in ion channel composition and resulting pharmacology in different nematodes, the importance of pursuing species-specific drug target research is emphasized.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2022)
Article
Multidisciplinary Sciences
Shivani Choudhary, Melanie Abongwa, Sudhanva S. Kashyap, Saurabh Verma, Gunnar R. Mair, Daniel Kulke, Richard J. Martin, Alan P. Robertson
Summary: In this study, a GluCls subunit from Brugia malayi was cloned and its pharmacological properties were investigated. The results showed that the receptor was regulated by the natural ligand L-glutamate and ivermectin, and had dual effects when exposed to nodulisporic acid. Furthermore, the unique pharmacological characteristics of this GluCls subunit could explain the variation in drug sensitivities observed in different nematode parasites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Parasitology
Sudhanva S. Kashyap, Mark A. McHugh, Alan P. Robertson, Richard J. Martin
Summary: Human and veterinary filarial nematode infections are a major health concern in tropical countries, and the current control and prophylaxis methods have limitations. This study found that diethylcarbamazine (DEC) can enhance the paralysis effect of emodepside in adult female Brugia malayi, suggesting a potential strategy to improve infection control.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2022)
Article
Agriculture, Dairy & Animal Science
Jacques Cabaret, Melodie Mercier, Maurice Mahieu, Gisele Alexandre
Summary: Parasites, particularly gastrointestinal nematodes (GINs), pose a significant health threat to tropical goat husbandry. However, the use of synthetic anthelmintics has led to the development of resistance, necessitating the need for targeted treatments. Simple indicators such as anemia, weight loss, and hair roughness can be used to identify animals in need of treatment. The promotion of these indicators and the support of agricultural advisory services are crucial for their successful implementation.
Article
Multidisciplinary Sciences
Patricia Izquierdo, Claude Charvet, Cedric Neveu, A. Christopher Green, John E. H. Tattersall, Lindy Holden-Dye, Vincent O'Connor
Summary: In this study, the nematode C. elegans was used as a model organism to investigate the neurotoxic effects of organophosphates, particularly paraoxon-ethyl. The authors found that modulation of acetylcholine receptor function can mitigate the toxic effects of organophosphate poisoning. Mutants with reduced acetylcholine receptor activity were identified as being more resistant to the toxic consequences of organophosphate intoxication.
Article
Parasitology
Paulius Baltrusis, Peter Halvarsson, Claude L. Charvet, Johan Hoglund
Summary: Parasitic sheep nematodes, especially Haemonchus contortus, cause significant damage to animals due to their drug resistance capability. However, the mechanism of resistance to compounds like levamisole and efficient resistance detection tools are still not well understood. In this study, the presence and frequency of a newly reported mutation associated with levamisole resistance were investigated in different isolates of H. contortus. The results suggest that the mutation causing the S168T substitution in hco-acr-8 may be a plausible variant associated with levamisole resistance in some isolates.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2023)
Article
Agriculture, Dairy & Animal Science
Eric R. Morgan, Anne Segonds-Pichon, Hubert Ferte, Patrick Duncan, Jacques Cabaret
Summary: Parasite overdispersion among hosts has important implications for their population dynamics and control. The factors determining parasite overdispersion, such as parasite acquisition and acquired host immunity, have not been thoroughly studied in parasite populations.
Article
Agriculture, Dairy & Animal Science
Caroline Chylinski, Jacques Cortet, Jacques Cabaret, Alexandra Blanchard
Summary: Gastrointestinal nematodes (GIN) utilize flexible life history strategies to adapt to environmental challenges, and their fitness can be maintained by adjusting subsequent life traits. Understanding how distinct populations of GIN species respond to environmental challenges is important for parasite control interventions. This study compared the life history traits and fitness outcomes of three Haemonchus contortus isolates exposed to challenges during different life stages. The findings demonstrate isolate-specific alterations to life history strategies and provide insights into non-genetic adaptive processes that may affect parasite control strategies.