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Anthelmintic resistance: markers for resistance, or susceptibility?

Published online by Cambridge University Press:  09 September 2010

R. N. BEECH ,
P. SKUCE ,
D. J. BARTLEY ,
R. J. MARTIN ,
R. K. PRICHARD  and
J. S. GILLEARD
R. N. BEECH*
Affiliation:
Institute of Parasitology, Macdonald College, McGill University, Ste Anne de Bellevue, QC, H9X 3V9 Canada
P. SKUCE
Affiliation:
Parasitology Division, Moredun Research Institute, Penicuik, Midlothian, EH26 0PZ, UK
D. J. BARTLEY
Affiliation:
Parasitology Division, Moredun Research Institute, Penicuik, Midlothian, EH26 0PZ, UK
R. J. MARTIN
Affiliation:
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA
R. K. PRICHARD
Affiliation:
Institute of Parasitology, Macdonald College, McGill University, Ste Anne de Bellevue, QC, H9X 3V9 Canada
J. S. GILLEARD
Affiliation:
Department Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada
*
*Corresponding author: Institute of Parasitology, Macdonald College, McGill University, Ste Anne de Bellevue, QC, H9X 3V9 Canada. Tel: + 514 398 7535. Fax: + 514 398 7857. E-mail: [email protected]
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Summary

The Consortium for Anthelmintic Resistance and Susceptibility (CARS) brings together researchers worldwide, with a focus of advancing knowledge of resistance and providing information on detection methods and treatment strategies. Advances in this field suggest mechanisms and features of resistance that are shared among different classes of anthelmintic. Benzimidazole resistance is characterized by specific amino acid substitutions in beta-tubulin. If present, these substitutions increase in frequency upon drug treatment and lead to treatment failure. In the laboratory, sequence substitutions in ion-channels can contribute to macrocyclic lactone resistance, but there is little evidence that they are significant in the field. Changes in gene expression are associated with resistance to several different classes of anthelmintic. Increased P-glycoprotein expression may prevent drug access to its site of action. Decreased expression of ion-channel subunits and the loss of specific receptors may remove the drug target. Tools for the identification and genetic analysis of parasitic nematodes and a new online database will help to coordinate research efforts in this area. Resistance may result from a loss of sensitivity as well as the appearance of resistance. A focus on the presence of anthelmintic susceptibility may be as important as the detection of resistance.

Keywords

anthelmintic resistancebenzimidazolemacrocyclic lactonelevamisolemonepantelligand-gated ion-channelP-glycoproteinbeta-tubulin
Type
Review Article
Information
Parasitology , Volume 138 , Issue 2 , February 2011 , pp. 160 - 174
Copyright
Copyright © Cambridge University Press 2010

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References

REFERENCES

Absalom, N. L., Lewis, T. M. and Schofield, P. R. (2004). Mechanisms of channel gating of the ligand-gated ion channel superfamily inferred from protein structure. Experimental Physiology 89, 145–153.CrossRefGoogle ScholarPubMed
Ardleli, B. F. and Prichard, R. K. (2004). Identification of variant ABC-transporter genes among Onchocerca volvulus collected from ivermectin-treated and untreated patients in Ghana, West Africa. Annals of Tropical Medicine and Parasitology 98, 371–384.Google Scholar
Ardleli, B. F., Stitt, L. E., Tompkins, J. B. and Prichard, R. K. (2009). A comparison of the effects of ivermectin and moxidectin on the nematode Caenorhabditis elegans. Veterinary Parasitology 165, 96–108.CrossRefGoogle Scholar
Ballivet, M., Alliod, C., Bertrand, S. and Bertrand, D. (1996). Nicotinic acetylcholine receptors in the nematode Caenorhabditis elegans. Journal of Molecular Biology 258, 261–269.CrossRefGoogle ScholarPubMed
Beech, R. N., Prichard, R. K. and Scott, M. E. (1994). Genetic variability of the beta-tubulin genes in benzimidazole-susceptible and -resistant strains of Haemonchus contortus. Genetics 138, 103–110.CrossRefGoogle ScholarPubMed
Beech, R. N. and Silvestre, A. (2010). Mutations associated with anthelmintic drug resistance. Anti-Infective Agents in Medicinal Chemistry 9, 105–112.CrossRefGoogle Scholar
Beech, R. N., Wolstenholme, A. J., Neveu, C. and Dent, J. A. (2010). Nematode parasite genes, what's in a name? Trends in Parasitology 26, 334–340.CrossRefGoogle Scholar
Berriman, M. (2009 a). The Haemonchus contortus sequencing project http://www.sanger.ac.uk/Projects/H_contortus/Google Scholar
Berriman, M. (2009 b). The Teladorsagia circumcincta sequencing project http://www.sanger.ac.uk/Projects/H_contortus/Google Scholar
Berriman, M., Haas, B. J., LoVerde, P. T., Wilson, R. A., Dillon, G. P., Cerqueira, G. C., Mashiyama, S. T., Al-Lazikani, B., Andrade, L. F., Ashton, P. D., Aslett, M. A., Bartholomeu, D. C., Blandin, G., Caffrey, C. R., Coghlan, A., Coulson, R., Day, T. A., Delcher, A., DeMarco, R., Djikeng, A., Eyre, T., Gamble, J. A., Ghedin, E., Gu, Y., Hertz-Fowler, C., Hirai, H., Hirai, Y., Houston, R., Ivens, A., Johnston, D. A., Lacerda, D., Macedo, C. D., McVeigh, P., Ning, Z., Oliveira, G., Overington, J. P., Parkhill, J., Pertea, M., Pierce, R. J., Protasio, A. V., Quail, M. A., Rajandream, M. A., Rogers, J., Sajid, M., Salzberg, S. L., Stanke, M., Tivey, A. R., White, O., Williams, D. L., Wortman, J., Wu, W., Zamanian, M., Zerlotini, A., Fraser-Liggett, C. M., Barrell, B. G. and El-Sayed, N. M. (2009). The genome of the blood fluke Schistosoma mansoni. Nature, London 460, 352–358.CrossRefGoogle ScholarPubMed
Bhargava, A. and Fuentes, F. F. (2010). Mutational dynamics of microsatellites. Molecular Biotechnology 44, 250–266.CrossRefGoogle ScholarPubMed
Blackhall, W. J., Prichard, R. K. and Beech, R. N. (2008). P-glycoprotein selection in strains of Haemonchus contortus resistant to benzimidazoles. Veterinary Parasitology 152, 101–107.CrossRefGoogle ScholarPubMed
Blaxter, M. L., De Ley, P., Garey, J. R., Liu, L. X., Scheldeman, P., Vierstraete, A., Vanfleteren, J. R., Mackey, L. Y., Dorris, M., Frisse, L. M., Vida, J. T. and Thomas, W. K. (1998). A molecular evolutionary framework for the phylum Nematoda. Nature, London 392, 71–75.CrossRefGoogle ScholarPubMed
Boulin, T., Gielen, M., Richmond, J. E., Williams, D. C., Paoletti, P. and Bessereau, J. L. (2008). Eight genes are required for functional reconstitution of the Caenorhabditis elegans levamisole-sensitive acetylcholine receptor. Proceedings of the National Academy of Sciences, USA 105, 18590–18595.CrossRefGoogle ScholarPubMed
Bourguinat, C., Ardelli, B. F., Pion, S. D., Kamgno, J., Gardon, J., Duke, B. O., Boussinesq, M. and Prichard, R. K. (2008). P-glycoprotein-like protein, a possible genetic marker for ivermectin resistance selection in Onchocerca volvulus. Molecular and Biochemical Parasitology 158, 101–111.CrossRefGoogle ScholarPubMed
Cabaret, J. (2008). Pro and cons of targeted selective treatment against digestive-tract strongyles of ruminants. Parasite 15, 506–509.CrossRefGoogle ScholarPubMed
Chen, C., Zhao, W., Lu, Y., Wang, J., Chen, Y., Li, H. and Zhou, M. (2009). High-throughput detection of highly benzimidazole-resistant allele E198A with mismatch primers in allele-specific real-time polymerase chain reaction. Pest Management Science 65, 413–419.CrossRefGoogle ScholarPubMed
Conder, G. A., Jen, L. W., Marbury, K. S., Johnson, S. S., Guimond, P. M., Thomas, E. M. and Lee, B. L. (1990). A novel anthelmintic model utilizing jirds, Meriones unguiculatus, infected with Haemonchus contortus. Journal of Parasitology 76, 168–170.CrossRefGoogle ScholarPubMed
Conder, G. A., Johnson, S. S., Guimond, P. M., Cox, D. L. and Lee, B. L. (1991 a). Concurrent infections with the ruminant nematodes Haemonchus contortus and Trichostrongylus colubriformis in jirds, Meriones unguiculatus, and use of this model for anthelmintic studies. Journal of Parasitology 77, 621–623.Google Scholar
Conder, G. A., Johnson, S. S., Guimond, P. M., Geary, T. G., Lee, B. L., Winterrowd, C. A., Lee, B. H. and DiRoma, P. J. (1991 b). Utility of a Haemonchus contortus/jird (Meriones unguiculatus) model for studying resistance to levamisole. Journal of Parasitology 77, 83–86.CrossRefGoogle ScholarPubMed
Crowe, M. L. (2005). SeqDoC: rapid SNP and mutation detection by direct comparison of DNA sequence chromatograms. BMC Bioinformatics 6, 133.CrossRefGoogle ScholarPubMed
Cully, D. F. and Paress, P. S. (1991). Solubilization and characterization of a high affinity ivermectin binding site from Caenorhabditis elegans. Molecular Pharmacology 40, 326–332.Google ScholarPubMed
Cvilink, V., Lamka, J. and Skalova, L. (2009). Xenobiotic metabolizing enzymes and metabolism of anthelminthics in helminths. Drug Metabolism Reviews 41, 8–26.Google Scholar
de Lourdes Mottier, M. and Prichard, R. K. (2008). Genetic analysis of a relationship between macrocyclic lactone and benzimidazole anthelmintic selection on Haemonchus contortus. Pharmacogenetics and Genomics 18, 129–140.Google Scholar
Dent, J. A., Smith, M. M., Vassilatis, D. K. and Avery, L. (2000). The genetics of ivermectin resistance in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, USA 97, 2674–2679.CrossRefGoogle ScholarPubMed
Diawara, A., Drake, L. J., Suswillo, R. R., Kihara, J., Bundy, D. A., Scott, M. E., Halpenny, C., Stothard, J. R. and Prichard, R. K. (2009). Assays to detect beta-tubulin codon 200 polymorphism in Trichuris trichiura and Ascaris lumbricoides. PLoS Neglected Tropical Diseases 3, e397.CrossRefGoogle ScholarPubMed
Driscoll, M., Dean, E., Reilly, E., Bergholz, E. and Chalfie, M. (1989). Genetic and molecular analysis of a Caenorhabditis elegans beta-tubulin that conveys benzimidazole sensitivity. Journal of Cell Biology 109, 2993–3003.CrossRefGoogle ScholarPubMed
Drudge, J. H., Szanto, J., Wyant, Z. N. and Elam, G. W. (1964). Field studies on parasite control of sheep: comparison of thiabendazole, ruelene and phenothiazine. American Journal of Veterinary Research 25, 1512–1518.Google Scholar
Fauvin, A., Charvet, C., Issouf, M., Cortet, J., Cabaret, J. and Neveu, C. (2010). cDNA-AFLP analysis in levamisole-resistant Haemonchus contortus reveals alternative splicing in a nicotinic acetylcholine receptor subunit. Molecular and Biochemical Parasitology 170, 105–107.CrossRefGoogle Scholar
Feng, X. P., Hayashi, J., Beech, R. N. and Prichard, R. K. (2002). Study of the nematode putative GABA type-A receptor subunits: evidence for modulation by ivermectin. Journal of Neurochemistry 83, 870–878.CrossRefGoogle ScholarPubMed
Forrester, S. G., Prichard, R. K. and Beech, R. N. (2002). A glutamate-gated chloride channel subunit from Haemonchus contortus: expression in a mammalian cell line, ligand binding, and modulation of anthelmintic binding by glutamate. Biochemical Pharmacology 63, 1061–1068.Google Scholar
Galazzo, D. (2004). A comparison of laboratory and field resistance to macrocyclic lactones in Haemonchus contortus. M.Sc. thesis. McGill University, Montreal, Canada.Google Scholar
Garg, R. and Yadav, C. L. (2008). Genotyping of benzimidazole susceptible and resistant alleles in different populations of Haemonchus contortus from Himalayan and sub-Himalayan regions of North-West India. Tropical Animal Health and Production 41, 1127–1131.CrossRefGoogle ScholarPubMed
Ghedin, E., Wang, S., Spiro, D., Caler, E., Zhao, Q., Crabtree, J., Allen, J. E., Delcher, A. L., Guiliano, D. B., Miranda-Saavedra, D., Angiuoli, S. V., Creasy, T., Amedeo, P., Haas, B., El-Sayed, N. M., Wortman, J. R., Feldblyum, T., Tallon, L., Schatz, M., Shumway, M., Koo, H., Salzberg, S. L., Schobel, S., Pertea, M., Pop, M., White, O., Barton, G. J., Carlow, C. K., Crawford, M. J., Daub, J., Dimmic, M. W., Estes, C. F., Foster, J. M., Ganatra, M., Gregory, W. F., Johnson, N. M., Jin, J., Komuniecki, R., Korf, I., Kumar, S., Laney, S., Li, B. W., Li, W., Lindblom, T. H., Lustigman, S., Ma, D., Maina, C. V., Martin, D. M., McCarter, J. P., McReynolds, L., Mitreva, M., Nutman, T. B., Parkinson, J., Peregrin-Alvarez, J. M., Poole, C., Ren, Q., Saunders, L., Sluder, A. E., Smith, K., Stanke, M., Unnasch, T. R., Ware, J., Wei, A. D., Weil, G., Williams, D. J., Zhang, Y., Williams, S. A., Fraser-Liggett, C., Slatko, B., Blaxter, M. L. and Scott, A. L. (2007). Draft genome of the filarial nematode parasite Brugia malayi. Science 317, 1756–1760.CrossRefGoogle ScholarPubMed
Ghisi, M., Kaminsky, R. and Maser, P. (2007). Phenotyping and genotyping of Haemonchus contortus isolates reveals a new putative candidate mutation for benzimidazole resistance in nematodes. Veterinary Parasitology 144, 313–320.Google Scholar
Gilleard, J. S. and Beech, R. N. (2007). Population genetics of anthelmintic resistance in parasitic nematodes. Parasitology 134, 1133–1147.Google Scholar
Grillo, V., Jackson, F., Cabaret, J. and Gilleard, J. S. (2007). Population genetic analysis of the ovine parasitic nematode Teladorsagia circumcincta and evidence for a cryptic species. International Journal for Parasitology 37, 435–447.CrossRefGoogle ScholarPubMed
Harhay, M. O., Horton, J. and Olliaro, P. L. (2010). Epidemiology and control of human gastrointestinal parasites in children. Expert Review of Anti Infective Therapy 8, 219–234.CrossRefGoogle ScholarPubMed
Hodgkinson, J. E., Clark, H. J., Kaplan, R. M., Lake, S. L. and Matthews, J. B. (2008). The role of polymorphisms at beta tubulin isotype 1 codons 167 and 200 in benzimidazole resistance in cyathostomins. International Journal for Parasitology 38, 1149–1160.Google Scholar
Hoglund, J., Gustafsson, K., Ljungstrom, B. L., Engstrom, A., Donnan, A. and Skuce, P. (2009). Anthelmintic resistance in Swedish sheep flocks based on a comparison of the results from the faecal egg count reduction test and resistant allele frequencies of the beta-tubulin gene. Veterinary Parasitology 161, 60–68.Google Scholar
Jablonka, E. and Raz, G. (2009). Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution. Quarterly Reviews in Biology 84, 131–176.CrossRefGoogle Scholar
James, C. E. and Davey, M. W. (2009). Increased expression of ABC transport proteins is associated with ivermectin resistance in the model nematode Caenorhabditis elegans. International Journal for Parasitology 39, 213–220.Google Scholar
James, C. E., Hudson, A. L. and Davey, M. W. (2009). Drug resistance mechanisms in helminths: is it survival of the fittest? Trends in Parasitology 25, 328–335.CrossRefGoogle ScholarPubMed
Jones, A. K., Davis, P., Hodgkin, J. and Sattelle, D. B. (2007). The nicotinic acetylcholine receptor gene family of the nematode Caenorhabditis elegans: an update on nomenclature. Invertebrate Neuroscience 7, 129–131.CrossRefGoogle ScholarPubMed
Kaminsky, R., Ducray, P., Jung, M., Clover, R., Rufener, L., Bouvier, J., Weber, S. S., Wenger, A., Wieland-Berghausen, S., Goebel, T., Gauvry, N., Pautrat, F., Skripsky, T., Froelich, O., Komoin-Oka, C., Westlund, B., Sluder, A. and Maser, P. (2008). A new class of anthelmintics effective against drug-resistant nematodes. Nature, London 452, 176–180.CrossRefGoogle ScholarPubMed
Kenyon, F., Greer, A. W., Coles, G. C., Cringoli, G., Papadopoulos, E., Cabaret, J., Berrag, B., Varady, M., Van Wyk, J. A., Thomas, E., Vercruysse, J. and Jackson, F. (2009). The role of targeted selective treatments in the development of refugia-based approaches to the control of gastrointestinal nematodes of small ruminants. Veterinary Parasitology 164, 3–11.CrossRefGoogle Scholar
Kopp, S. R., Coleman, G. T., Traub, R. J., McCarthy, J. S. and Kotze, A. C. (2009). Acetylcholine receptor subunit genes from Ancylostoma caninum: altered transcription patterns associated with pyrantel resistance. International Journal for Parasitology 39, 435–441.CrossRefGoogle ScholarPubMed
Kotze, A. C., Dobson, R. J., Tyrrell, K. L. and Stein, P. A. (2002). High-level ivermectin resistance in a field isolate of Haemonchus contortus associated with a low level of resistance in the larval stage: implications for resistance detection. Veterinary Parasitology 108, 255–263.Google Scholar
Kotze, A. C., Le Jambre, L. F. and O'Grady, J. (2006). A modified larval migration assay for detection of resistance to macrocyclic lactones in Haemonchus contortus, and drug screening with Trichostrongylidae parasites. Veterinary Parasitology 137, 294–305.CrossRefGoogle ScholarPubMed
Krause, R. M., Buisson, B., Bertrand, S., Corringer, P. J., Galzi, J. L., Changeux, J. P. and Bertrand, D. (1998). Ivermectin: a positive allosteric effector of the alpha7 neuronal nicotinic acetylcholine receptor. Molecular Pharmacology 53, 283–294.CrossRefGoogle ScholarPubMed
Kwa, M. S. G., Jetty, V. S. and Roos, M. H. (1994). Benzimidazole resistance in Haemonchus contortus is correlated with a conserved mutation at amino acid 200 in ß-tubulin isotype 1. Molecular and Biochemical Parasitology 63, 299–303.CrossRefGoogle Scholar
Le Jambre, L. F. (1993). Ivermectin-resistant Haemonchus contortus in Australia. Australian Veterinary Journal 70, 357.Google Scholar
Liu, F., Zhou, Y., Wang, Z. Q., Lu, G., Zheng, H., Brindley, P. J., McManus, D. P., Blair, D., Zhang, Q. H., Zhong, Y., Wang, S., Han, Z. G. and Chen, Z. (2009). The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature, London 460, 345–351.Google Scholar
Martin, R. J. (1996). An electrophysiological preparation of Ascaris suum pharyngeal muscle reveals a glutamate-gated chloride channel sensitive to the avermectin analogue, milbemycin D. Parasitology 112, 247–252.CrossRefGoogle Scholar
Martin, R. J., Clark, C. L., Trailovic, S. M. and Robertson, A. P. (2004). Oxantel is an N-type (methyridine and nicotine) agonist not an L-type (levamisole and pyrantel) agonist: classification of cholinergic anthelmintics in Ascaris. International Journal for Parasitology 34, 1083–1090.CrossRefGoogle Scholar
Martin, R. J. and Pennington, A. J. (1989). A patch-clamp study of effects of dihydroavermectin on Ascaris muscle. British Journal of Pharmacolology 98, 747–756.CrossRefGoogle ScholarPubMed
McCavera, S., Rogers, A. T., Yates, D. M., Woods, D. J. and Wolstenholme, A. J. (2009). An ivermectin-sensitive glutamate-gated chloride channel from the parasitic nematode Haemonchus contortus. Molecular Pharmacology 75, 1347–1355.CrossRefGoogle ScholarPubMed
McCavera, S., Walsh, T. K. and Wolstenholme, A. J. (2007). Nematode ligand-gated chloride channels: an appraisal of their involvement in macrocyclic lactone resistance and prospects for developing molecular markers. Parasitology 134, 1111–1121.Google Scholar
Merino, G., Real, R., Baro, M. F., Gonzalez-Lobato, L., Prieto, J. G., Alvarez, A. I. and Marques, M. M. (2009). Natural allelic variants of bovine ATP-binding cassette transporter ABCG2: increased activity of the Ser581 variant and development of tools for the discovery of new ABCG2 inhibitors. Drug Metababolism and Disposition 37, 5–9.CrossRefGoogle ScholarPubMed
Mes, T. H. (2004). Purifying selection and demographic expansion affect sequence diversity of the ligand-binding domain of a glutamate-gated chloride channel gene of Haemonchus placei. Journal of Molecular Evolution 58, 466–478.CrossRefGoogle ScholarPubMed
Mitani, Y., Lezhava, A., Kawai, Y., Kikuchi, T., Oguchi-Katayama, A., Kogo, Y., Itoh, M., Miyagi, T., Takakura, H., Hoshi, K., Kato, C., Arakawa, T., Shibata, K., Fukui, K., Masui, R., Kuramitsu, S., Kiyotani, K., Chalk, A., Tsunekawa, K., Murakami, M., Kamataki, T., Oka, T., Shimada, H., Cizdziel, P. E. and Hayashizaki, Y. (2007). Rapid SNP diagnostics using asymmetric isothermal amplification and a new mismatch-suppression technology. Nature Methods 4, 257–262.CrossRefGoogle Scholar
Molento, M. B. (2009). Parasite control in the age of drug resistance and changing agricultural practices. Veterinary Parasitology 163, 229–234.CrossRefGoogle ScholarPubMed
Molento, M. B., Wang, G. T. and Prichard, R. K. (1999). Decreased ivermectin and moxidectin sensitivity in Haemonchus contortus selected with moxidectin over 14 generations. Veterinary Parasitology 86, 77–81.Google Scholar
Munoz, C., Gomez Talquenca, S. and Volpe, M. L. (2009). Tetra primer ARMS-PCR for identification of SNP in beta-tubulin of Botrytis cinerea, responsible of resistance to benzimidazole. Journal of Microbial Methods 78, 245–246.CrossRefGoogle ScholarPubMed
Neveu, C., Charvet, C., Fauvin, A., Cortet, J., Beech, R. and Cabaret, J. (2010). Genetic diversity of levamisole receptor subunits in parasitic nematodes and abbreviated transcripts associated with resistance. Pharmacogenetics and Genomics 20, 414–425.CrossRefGoogle ScholarPubMed
Njue, A. I. and Prichard, R. K. (2004). Genetic variability of glutamate-gated chloride channel genes in ivermectin-susceptible and -resistant strains of Cooperia oncophora. Parasitology 129, 741–751.CrossRefGoogle ScholarPubMed
Palcy, C., Silvestre, A., Sauve, C., Cortet, J. and Cabaret, J. (2008). Benzimidazole resistance in Trichostrongylus axei in sheep: Long-term monitoring of affected sheep and genotypic evaluation of the parasite. Veterinary Journal 183, 68–74.Google Scholar
Puttachary, S., Robertson, A. P., Clark, C. L. and Martin, R. J. (2010). Levamisole and ryanodine receptors. II: An electrophysiological study in Ascaris suum. Molecular and Biochemical Parasitology 171, 8–16.Google Scholar
Qian, H., Martin, R. J. and Robertson, A. P. (2006). Pharmacology of N-, L-, and B-subtypes of nematode nAChR resolved at the single-channel level in Ascaris suum. FASEB Journal 20, 2606–2608.CrossRefGoogle Scholar
Qian, H., Robertson, A. P., Powell-Coffman, J. A. and Martin, R. J. (2008). Levamisole resistance resolved at the single-channel level in Caenorhabditis elegans. FASEB Journal 22, 3247–3254.CrossRefGoogle ScholarPubMed
Rao, V. T., Siddiqui, S. Z., Prichard, R. K. and Forrester, S. G. (2009). A dopamine-gated ion channel (HcGGR3*) from Haemonchus contortus is expressed in the cervical papillae and is associated with macrocyclic lactone resistance. Molecular and Biochemical Parasitology 166, 54–61.CrossRefGoogle ScholarPubMed
Redman, E., Grillo, V., Saunders, G., Packard, E., Jackson, F., Berriman, M. and Gilleard, J. S. (2008 a). Genetics of mating and sex determination in the parasitic nematode Haemonchus contortus. Genetics 180, 1877–1887.Google Scholar
Redman, E., Packard, E., Grillo, V., Smith, J., Jackson, F. and Gilleard, J. S. (2008 b). Microsatellite analysis reveals marked genetic differentiation between Haemonchus contortus laboratory isolates and provides a rapid system of genetic fingerprinting. International Journal for Parasitology 38, 111–122.CrossRefGoogle ScholarPubMed
Robertson, A. P., Bjorn, H. E. and Martin, R. J. (1999). Resistance to levamisole resolved at the single-channel level. FASEB Journal 13, 749–760.Google Scholar
Robertson, A. P., Clark, C. L., Burns, T. A., Thompson, D. P., Geary, T. G., Trailovic, S. M. and Martin, R. J. (2002). Paraherquamide and 2-deoxy-paraherquamide distinguish cholinergic receptor subtypes in Ascaris muscle. Journal of Pharmacology and Experimental Therapeutics 302, 853–860.Google Scholar
Robertson, A. P., Clark, C. L. and Martin, R. J. (2010). Levamisole and ryanodine receptors. I: A contraction study in Ascaris suum. Molecular and Biochemical Parasitology 171, 1–7.CrossRefGoogle Scholar
Ronaghi, M., Uhlen, M. and Nyren, P. (1998). A sequencing method based on real-time pyrophosphate. Science 281, 363–365.CrossRefGoogle ScholarPubMed
Rufener, L., Kaminsky, R. and Maser, P. (2009 a). In vitro selection of Haemonchus contortus for benzimidazole resistance reveals a mutation at amino acid 198 of beta-tubulin. Molecular and Biochemical Parasitology 168, 120–122.Google Scholar
Rufener, L., Maser, P., Roditi, I. and Kaminsky, R. (2009 b). Haemonchus contortus acetylcholine receptors of the DEG-3 subfamily and their role in sensitivity to monepantel. PLoS Pathogens 5, e1000380.Google Scholar
Saragoza, P. A., Modir, J. G., Goel, N., French, K. L., Li, L., Nowak, M. W. and Stitzel, J. A. (2003). Identification of an alternatively processed nicotinic receptor alpha7 subunit RNA in mouse brain. Brain Research Molecular Brain Research 117, 15–26.Google Scholar
Schwenkenbecher, J. M., Albonico, M., Bickle, Q. and Kaplan, R. M. (2007). Characterization of beta-tubulin genes in hookworms and investigation of resistance-associated mutations using real-time PCR. Molecular and Biochemical Parasitology 156, 167–174.Google Scholar
Schwenkenbecher, J. M. and Kaplan, R. M. (2009). Real-time PCR assays for monitoring benzimidazole resistance associated mutations in Ancylostoma caninum. Experimental Parasitology 122, 6–10.CrossRefGoogle ScholarPubMed
Silvestre, A. and Cabaret, J. (2002). Mutation in position 167 of isotype 1 beta-tubulin gene of Trichostrongylid nematodes: role in benzimidazole resistance? Molecular and Biochemical Parasitology 120, 297–300.Google Scholar
Silvestre, A. and Humbert, J. F. (2002). Diversity of benzimidazole-resistance alleles in populations of small ruminant parasites. International Journal for Parasitology 32, 921–928.CrossRefGoogle ScholarPubMed
Silvestre, A., Sauve, C., Cortet, J. and Cabaret, J. (2009). Contrasting genetic structures of two parasitic nematodes, determined on the basis of neutral microsatellite markers and selected anthelmintic resistance markers. Molecular Ecology 18, 5086–5100.CrossRefGoogle ScholarPubMed
Sotirchos, I. M., Hudson, A. L., Ellis, J. and Davey, M. W. (2008). Thioredoxins of a parasitic nematode: comparison of the 16- and 12-kDA thioredoxins from Haemonchus contortus. Free Radical Biology and Medicine 44, 2026–2033.Google Scholar
Varady, M., Corba, J., Letkova, V. and Kovac, G. (2009). Comparison of two versions of larval development test to detect anthelmintic resistance in Haemonchus contortus. Veterinary Parasitology 160, 267–271.CrossRefGoogle ScholarPubMed
Von Samson-Himmelstjerna, G., Blackhall, W. J., McCarthy, J. S. and Skuce, P. J. (2007). Single nucleotide polymorphism (SNP) markers for benzimidazole resistance in veterinary nematodes. Parasitology 134, 1077–1086.Google Scholar
Von Samson-Himmelstjerna, G., Walsh, T. K., Donnan, A. A., Carriere, S., Jackson, F., Skuce, P. J., Rohn, K. and Wolstenholme, A. J. (2009). Molecular detection of benzimidazole resistance in Haemonchus contortus using real-time PCR and pyrosequencing. Parasitology 136, 349–358.Google Scholar
Walsh, T. K., Donnan, A. A., Jackson, F., Skuce, P. and Wolstenholme, A. J. (2007). Detection and measurement of benzimidazole resistance alleles in Haemonchus contortus using real-time PCR with locked nucleic acid Taqman probes. Veterinary Parasitology 144, 304–312.CrossRefGoogle ScholarPubMed
Webster, L. M., Johnson, P. C., Adam, A., Mable, B. K. and Keller, L. F. (2008) Absence of three known benzimidazole resistance mutations in Trichostrongylus tenuis, a nematode parasite of avian hosts. Veterinary Parasitology 158, 302–310.CrossRefGoogle ScholarPubMed
Williamson, S. M., Robertson, A. P., Brown, L., Williams, T., Woods, D. J., Martin, R. J., Sattelle, D. B. and Wolstenholme, A. J. (2009). The nicotinic acetylcholine receptors of the parasitic nematode Ascaris suum: formation of two distinct drug targets by varying the relative expression levels of two subunits. PLoS Pathogens 5, e1000517.Google Scholar
Ye, S., Dhillon, S., Ke, X., Collins, A. R. and Day, I. N. (2001). An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Research 29, E88–8.Google Scholar