Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-20T13:19:19.625Z Has data issue: false hasContentIssue false
  • English
  • Français

Single nucleotide polymorphism (SNP) markers for benzimidazole resistance in veterinary nematodes

Published online by Cambridge University Press:  03 July 2007

G. VON SAMSON-HIMMELSTJERNA ,
W. J. BLACKHALL ,
J. S. McCARTHY  and
P. J. SKUCE
G. VON SAMSON-HIMMELSTJERNA*
Affiliation:
Institute for Parasitology, University of Veterinary Medicine Foundation, Bünteweg 17, Hannover 30559, Germany
W. J. BLACKHALL
Affiliation:
Institute for Parasitology, University of Veterinary Medicine Foundation, Bünteweg 17, Hannover 30559, Germany
J. S. McCARTHY
Affiliation:
Queensland Institute of Medical Research, University of Queensland, Herston QLD 4006, Australia
P. J. SKUCE
Affiliation:
Moredun Research Institute, Pentlands Science Park, Edinburgh EH26 0PZ, UK
*
*Corresponding author: Institute for Parasitology, University of Veterinary Medicine Foundation, Bünteweg 17, Hannover 30559, Germany. Tel: +49 511 953 8557. Fax: +49 511 953 8555. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Resistance to the benzimidazole class of anthelmintics in nematodes of veterinary importance has a long history. Research into the mechanisms responsible for this resistance is subsequently at a more advanced stage than for other classes of anthelmintics. The principal mechanism of resistance to benzimidazoles is likely to involve changes in the primary structure of β-tubulins, the building blocks of microtubules. Specifically, point mutations in the β-tubulin isotype 1 gene leading to amino acid substitutions in codons 167, 198, and 200 of the protein have been associated with resistance in nematodes. These single nucleotide polymorphisms offer a means of detecting the presence of resistance within populations. In this mini-review, we focus on the prevalence and importance of these polymorphisms in three groups of nematodes: trichostrongylids, cyathostomins, and hookworms. A brief overview of existing strategies for genotyping single nucleotide polymorphisms is also presented. The CARS initiative hopes to exploit these known polymorphisms to further our understanding of the phenomenon of BZ resistance.

Keywords

BenzimidazoleresistanceSNPtrichostrongylidcyathostominhookworm
Type
Research Article
Information
Parasitology , Volume 134 , Special Issue 8: MARKERS FOR ANTHELMINTIC RESISTANCE , August 2007 , pp. 1077 - 1086
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Albonico, M., Bickle, Q., Ramsan, M., Montresor, A., Savioli, L. and Taylor, M. (2003). Efficacy of mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted mebendazole treatment in Zanzibar. Bulletin of the World Health Organization 81, 343–352.Google ScholarPubMed
Albonico, M., Wright, V. and Bickle, Q. (2004). Molecular analysis of the beta-tubulin gene of human hookworms as a basis for possible benzimidazole resistance on Pemba Island. Molecular and Biochemical Parasitology 134, 281–284.CrossRefGoogle ScholarPubMed
Álvarez-Sánchez, M. A., Pérez-García, J., Cruz-Rojo, M. A. and Rojo-Vázquez, F. A. (2005). Real time PCR for the diagnosis of benzimidazole resistance in trichostrongylids of sheep. Veterinary Parasitology 129, 291–298.CrossRefGoogle ScholarPubMed
Blackhall, W. J., Drogemuller, M., Schnieder, T. and Samson-Himmelstjerna, G. VON (2006). Expression of recombinant β-tubulin alleles from Cylicocyclus nassatus (Cyathostominae). Parasitology Research 99, 687–693.CrossRefGoogle ScholarPubMed
Caviston, J. P. and Holzbaur, E. L. (2006). Microtubule motors at the intersection of trafficking and transport. Trends in Cell Biology 16, 530–537.CrossRefGoogle ScholarPubMed
Cirak, V. Y., Gulegen, E. and Bauer, C. (2004). Benzimidazole resistance in cyathostomin populations on horse farms in western Anatolia, Turkey. Parasitology Research 93, 392–395.CrossRefGoogle ScholarPubMed
Clark, H. J., Kaplan, R. M., Matthews, J. B. and Hodgkinson, J. E. (2005). Isolation and characterisation of a beta tubulin isotype 2 gene from two species of cyathostomin. International Journal for Parasitology 35, 349–358.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
De Clercq, D., Sacko, M., Behnke, J., Gilbert, F., Dorny, P. and Vercruysse, J. (1997). Failure of mebendazole in treatment of human hookworm infections in the southern region of Mali. American Journal of Tropical Medicine and Hygiene 57, 25–30.CrossRefGoogle ScholarPubMed
Drogemuller, M., Failing, K., Schnieder, T. and Samson-Himmelstjerna, G. VON (2004). Effect of repeated benzimidazole treatments with increasing dosages on the phenotype of resistance and the beta-tubulin codon 200 genotype distribution in a benzimidazole-resistant cyathostomin population. Veterinary Parasitology 123, 201–213.CrossRefGoogle Scholar
Drogemuller, M., Schnieder, T. and Samson-Himmelstjerna, G. VON (2004). Beta-tubulin complementary DNA sequence variations observed between cyathostomins from benzimidazole-susceptible and -resistant populations. Journal of Parasitology 90, 868–890.CrossRefGoogle ScholarPubMed
Elard, L. and Humbert, J. F. (1999). Importance of the mutation of amino acid 200 of the isotype-1 β-tubulin gene in the benzimidazole-resistance of the small-ruminant parasite, Teladorsagia circumcincta. Parasitology Research 85, 452–456.CrossRefGoogle ScholarPubMed
Elard, L., Cabaret, J. and Humbert, J. F. (1999). PCR diagnosis of benzimidazole-susceptibility or -resistance in natural populations of the small ruminant parasite, Teladorsagia circumcincta. Veterinary Parasitology 80, 231–237.CrossRefGoogle ScholarPubMed
Elard, L., Sauve, C. and Humbert, J. F. (1998). Fitness of benzimidazole-resistant and -susceptible worms of Teladorsagia circumcincta, a nematode parasite of small ruminants. Parasitology 117, 571–578.CrossRefGoogle ScholarPubMed
Geary, T. G., Nulf, S. C., Favreau, M. A., Tang, L., Prichard, R. K., Hatzenbuhler, N. T., Shea, M. H., Alexander, S. J. and Klein, R. D. (1992). Three beta-tubulin cDNAs from the parasitic nematode Haemonchus contortus. Molecular and Biochemical Parasitology 50, 295–306.CrossRefGoogle ScholarPubMed
Geerts, S. and Gryseels, B. (2000). Drug resistance in human helminths: current situation and lessons from livestock. Clinical Microbiology Reviews 13, 207–222.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.CrossRefGoogle ScholarPubMed
Grant, W. N. and Mascord, L. J. (1996). Beta-tubulin gene polymorphism and benzimidazole resistance in Trichostrongylus colubriformis. International Journal for Parasitology 26, 71–77.CrossRefGoogle ScholarPubMed
Hotez, P. J., Molyneux, D. H., Fenwick, A., Ottesen, E., Ehrlich Sachs, S. and Sachs, J. D. (2006). Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PLoS Medicine 3, e102.CrossRefGoogle ScholarPubMed
Humbert, J. F., Cabaret, J., Elard, L., Leignel, V. and Silvestre, A. (2001). Molecular approaches to studying benzimidazole resistance in trichostrongylid nematode parasites of small ruminants. Veterinary Parasitology 101, 405–414.CrossRefGoogle ScholarPubMed
Jackson, R. A., Townsend, K. G., Pyke, C. and Lance, D. M. (1995). Isolation of oxfendazole resistant Cooperia oncophora in cattle. New Zealand Veterinary Journal 35, 187–189.CrossRefGoogle Scholar
Kaplan, R. M., Klei, T. R., Lyons, E. T., Lester, G., Courtney, C. H., French, D. D., Tolliver, S. C., Vidyashankar, A. N. and Zhao, Y. (2004). Prevalence of anthelmintic resistant cyathostomes on horse farms. Journal of the American Veterinary Medical Association 225, 903–910.CrossRefGoogle ScholarPubMed
Kaplan, R. M., Tolliver, S. C., Lyons, E. T., Chapman, M. R. and Klei, T. R. (2000). Characterization of β-tubulin genes from cyathostome populations with differing sensitivities to benzimidazole anthelmintics. In Proceedings of 45th Annual Meeting of the American Association of Veterinary Parasitologists, Salt Lake City, Utah, July 22–25, 2000, p. 82.Google Scholar
Kopp, S. R., Kotze, A. C., McCarthy, J. S. and Coleman, G. T. (2007). High-level pyrantel resistance in the hookworm Ancylostoma caninum. Veterinary Parasitology 143, 299–304.CrossRefGoogle ScholarPubMed
Kwa, M. S., Kooyman, F. N., Boersema, J. H. and Roos, M. H. (1993). Effect of selection for benzimidazole resistance in Haemonchus contortus on β-tubulin isotype 1 and isotype 2 genes. Biochemical and Biophysical Research Communications 191, 413–419.CrossRefGoogle ScholarPubMed
Kwa, M. S., Veenstra, J. G. and Roos, M. H. (1993). Molecular characterisation of β-tubulin genes present in benzimidazole-resistant populations of Haemonchus contortus. Molecular and Biochemical Parasitology 60, 133–143.CrossRefGoogle ScholarPubMed
Kwa, M. S., Veenstra, J. G. and Roos, M. H. (1994). Benzimidazole resistance in Haemonchus contortus is correlated with a conserved mutation at amino acid 200 in β-tubulin isotype 1. Molecular and Biochemical Parasitology 63, 299–303.CrossRefGoogle ScholarPubMed
Kwa, M. S., Veenstra, J. G., Van Dijk, M. and Roos, M. H. (1995). β-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. Journal of Molecular Biology 246, 500–510.CrossRefGoogle ScholarPubMed
Lacey, E. (1988). The role of the cytoskeletal protein, tubulin, in the mode of action and mechanism of drug resistance to benzimidazoles. International Journal for Parasitology 18, 885–936.CrossRefGoogle ScholarPubMed
Li, J., Katiyar, S. K. and Edlind, E. T. (1996). Site-directed mutagenesis of Saccharomyces cerevisiae β-tubulin: interaction between residue 167 and benzimidazole compounds. FEBS Letters 385, 7–10.CrossRefGoogle ScholarPubMed
Lubega, G. W. and Prichard, R. K. (1991). Interaction of benzimidazole anthelmintics with Haemonchus contortus tubulin: binding affinity and anthelmintic efficacy. Experimental Parasitology 73, 203–213.CrossRefGoogle ScholarPubMed
Margolis, R. L. and Wilson, L. (1998). Microtubule treadmilling: what goes around comes around. Bioessays 20, 830–836.3.0.CO;2-N>CrossRefGoogle ScholarPubMed
Martin, P. J., Anderson, N. and Jarrett, R. G. (1989). Detecting benzimidazole resistance with faecal egg count reduction tests and in vitro assays. Australian Veterinary Journal 66, 236–240.CrossRefGoogle ScholarPubMed
Martin, R. J., Verma, S., Levandoski, M., Clark, C. L., Qian, H., Stewart, M. and Robertson, A. P. (2005). Drug resistance and neurotransmitter receptors of nematodes: recent studies on the mode of action of levamisole. Parasitology 131, S71–S84.CrossRefGoogle ScholarPubMed
McKenna, P. B. (1996). Anthelmintic resistance in cattle nematodes in New Zealand, is it increasing? New Zealand Veterinary Journal 44, 76.CrossRefGoogle ScholarPubMed
Meier, A. and Hertzberg, H. (2005). Equine strongyles II. Occurrence of anthelmintic resistance in Switzerland. Schweizer Archiv für Tierheilkunde 147, 389–396.CrossRefGoogle ScholarPubMed
Newton-Cheh, C. and Hirschhorn, J. N. (2005). Genetic association studies of complex traits: design and analysis issues. Mutation Research 573, 54–69.CrossRefGoogle ScholarPubMed
Njue, A. I. and Prichard, R. K. (2003). Cloning two full-length beta-tubulin isotype cDNAs from Cooperia oncophora, and screening for benzimidazole-associated mutations in two isolates. Parasitology 127, 579–588.CrossRefGoogle ScholarPubMed
Orbach, M. J., Porro, E. B. and Yanofsky, C. (1986). Cloning and characterization of the gene for β-tubulin from a benomyl-resistant mutant of Neurospora crassa and its use as a dominant selectable marker. Molecular and Cell Biology 6, 2452–2461.Google ScholarPubMed
Ottesen, E. A. (2006). Lymphatic filariasis: Treatment, control and elimination. Advances in Parasitology 61, 395–441.CrossRefGoogle ScholarPubMed
Pape, M., Posedi, J., Failing, K., Schnieder, T. and Samson-Himmelstjerna, G. VON (2003). Analysis of the beta-tubulin codon 200 genotype distribution in a benzimidazole-susceptible and -resistant cyathostome population. Parasitology 127, 53–59.CrossRefGoogle Scholar
Pape, M., Samson-Himmelstjerna, G. VON and Schnieder, T. (1999). Characterisation of the beta-tubulin gene of Cylicocyclus nassatus. International Journal for Parasitology 29, 1941–1947.CrossRefGoogle ScholarPubMed
Pape, M., Schnieder, T. and Samson-Himmelstjerna, G. VON (2002). Investigation of diversity and isotypes of the beta-tubulin cDNA in several small strongyle (Cyathostominae) species. Journal of Parasitology 88, 673–677.CrossRefGoogle ScholarPubMed
Prichard, R. K. (2001). Genetic variability following selection of Haemonchus contortus with anthelmintics. Trends in Parasitology 17, 445–453.CrossRefGoogle ScholarPubMed
Prichard, R. K. (2002). Benzimidazole binding to Haemonchus contortus tubulin: a question of structure. Trends in Parasitology 18, 3.CrossRefGoogle Scholar
Prichard, R. K., Oxberry, M., Bounhas, Y., Sharma, S., Lubega, G. and Geary, T. (2000). Polymerisation and benzimidazole binding assays with recombinant α- and β-tubulins from Haemonchus contortus. American Association of Veterinary Parasitologists. Forty-fifth Annual Meeting.Google Scholar
Reynoldson, J. A., Behnke, J. M., Pallant, L. J., Macnish, M. G., Gilbert, F., Giles, S., Spargo, R. J. and Thompson, R. C. (1997). Failure of pyrantel in treatment of human hookworm infections (Ancylostoma duodenale) in the Kimberley region of North West Australia. Acta Tropica 68, 301–312.CrossRefGoogle ScholarPubMed
Robinson, M., Trudgett, A., Fairweather, I. and McFerran, N. (2002). Benzimidazole binding to Haemonchus contortus tubulin: a question of structure. Trends in Parasitology 18, 153–154.CrossRefGoogle ScholarPubMed
Robinson, M. W., McFerran, N., Trudgett, A., Hoey, L. and Fairweather, I. (2004). A possible model of benzimidazole binding to beta-tubulin disclosed by invoking an interdomain movement. Journal of Molecular Graphics and Modelling 23, 275–284.CrossRefGoogle Scholar
Roos, M. H., Boersema, J. H., Borgsteede, F. H. M., Cornelissen, J., Taylor, M. and Ruitenberg, E. J. (1990). Molecular analysis of selection for benzimidazole resistance in the sheep parasite Haemonchus contortus. Molecular and Biochemical Parasitology 43, 77–88.CrossRefGoogle ScholarPubMed
Roos, M. H., Kwa, M. S. G. and Grant, W. N. (1995). New genetic and practical implications of selection for anthelmintic resistance in parasitic nematodes. Parasitology Today 11, 148–150.CrossRefGoogle Scholar
Samson-Himmelstjerna, G. VON and Blackhall, W. J. (2005). Will technology provide solutions for drug resistance in veterinary helminths? Veterinary Parasitology 132, 223–239.CrossRefGoogle Scholar
Samson-Himmelstjerna, G. VON, Buschbaum, S., Wirtherle, N., Pape, M. and Schnieder, T. (2003). TaqMan minor groove binder real-time PCR analysis of β-tubulin codon 200 polymorphism in small strongyles (Cyathostomin) indicates that the TAC allele is only moderately selected in benzimidazole-resistant populations. Parasitology 127, 489–496.CrossRefGoogle Scholar
Samson-Himmelstjerna, G. VON, Harder, A., Pape, M. and Schnieder, T. (2001). Novel small strongyle (Cyathostominae) beta-tubulin sequences. Parasitology Research 87, 122–125.CrossRefGoogle Scholar
Samson-Himmelstjerna, G. VON, Pape, M., von Witzendorff, C. and Schnieder, T. (2002 a). Allele-specific PCR for the beta-tubulin codon 200 TTC/TAC polymorphism using single adult and larval small strongyle (Cyathostominae) stages. Journal of Parasitology 88, 254–257.CrossRefGoogle Scholar
Samson-Himmelstjerna, G. VON, Witzendorff, C. VON, Sievers, G. and Schnieder, T. (2002 b). Comparative use of faecal egg count reduction test, egg hatch assay and beta-tubulin codon 200 genotyping in small strongyles (cyathostominae) before and after benzimidazole treatment. Veterinary Parasitology 108, 227–235.CrossRefGoogle Scholar
Schwab, A. E., Boakye, D. A., Kyelem, D. and Prichard, R. K. (2005). Detection of benzimidazole resistance-associated mutations in the filarial nematode Wuchereria bancrofti and evidence for selection by albendazole and ivermectin combination treatment. American Journal of Tropical Medicine and Hygiene 73, 234–238.CrossRefGoogle ScholarPubMed
Shayan, P., Eslami, A. and Hassan, B. (2007). Innovative restriction site created PCR-RFLP for detection of benzimidazole resistance in Teladorsagia circumcincta. Parasitology Research 100, 1063–1068.CrossRefGoogle ScholarPubMed
Silvestre, A. and Cabaret, J. (2002). Mutation in position 167 of isotype 1 β-tubulin gene of Trichostrongylid nematodes: role in benzimidazole resistance? Molecular and Biochemical Parasitology 120, 297–300.CrossRefGoogle ScholarPubMed
Silvestre, A. and Humbert, J. F. (2000). A molecular tool for species identification and benzimidazole resistance diagnosis in larval communities of small ruminant parasites. Experimental Parasitology 95, 271–276.CrossRefGoogle ScholarPubMed
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
Thomas, J. H., Neff, N. F. and Botstein, D. (1985). Isolation and characterization of mutations in the β-tubulin gene of Saccharomyces cerevisiae. Genetics 111, 715–734.CrossRefGoogle ScholarPubMed
Tiwari, J., Kumar, S., Kolte, A. P., Swarnkar, C. P., Singh, D. and Pathak, K. M. L. (2006). Detection of benzimidazole resistance in Haemonchus contortus using RFLP-PCR technique. Veterinary Parasitology 138, 301–307.CrossRefGoogle ScholarPubMed
Troell, K., Mattsson, J. G., Alderborn, A. and Hoglund, J. (2003). Pyrosequencing analysis identifies discrete populations of Haemonchus contortus from small ruminants. International Journal for Parasitology 33, 765–771.CrossRefGoogle ScholarPubMed
Varady, M., Konigova, A. and Corba, J. (2000). Benzimidazole resistance in equine cyathostomes in Slovakia. Veterinary parasitology 94, 67–74.CrossRefGoogle ScholarPubMed
Walsh, T. K., Donnan, A. A., Jackson, F., Skuce, P. J. 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
Wilson, L., Panda, D. and Jordan, M. A. (1999). Modulation of microtubule dynamics by drugs: a paradigm for the actions of cellular regulators. Cell Structure and Function 24, 329–335.CrossRefGoogle ScholarPubMed
Winterrowd, C. A., Pomroy, W. E., Sangster, N. C., Johnson, S. S. and Geary, T. G. (2003). Benzimidazole-resistant β-tubulin alleles in a population of parasitic nematodes (Cooperia oncophora). Veterinary Parasitology 117, 161–172.CrossRefGoogle Scholar
Wirtherle, N., Schnieder, T. and Samson-Himmelstjerna, G. VON (2004). Prevalence of benzimidazole resistance on horse farms in Germany. Veterinary Record 154, 39–41.CrossRefGoogle ScholarPubMed
Wolstenholme, A. J., Fairweather, I., Prichard, R. K., Samson-Himmelstjerna, G. VON and Sangster, N. C. (2004). Drug resistance in veterinary helminths. Trends in Parasitology 20, 469–476.CrossRefGoogle ScholarPubMed