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Albendazole resistance induced in Ancylostoma ceylanicum is not due to single-nucleotide polymorphisms (SNPs) at codons 167, 198, or 200 of the beta-tubulin gene, indicating another resistance mechanism

  • Luis Fernando Viana Furtado
  • Pedro Henrique Nascimento de Aguiar
  • Luciana Werneck Zuccherato
  • Talita Tatiana Guimarães Teixeira
  • William Pereira Alves
  • Vivian Jordania da Silva
  • Robin B Gasser
  • Élida Mara Leite RabeloEmail author
Helminthology - Original Paper
  • 46 Downloads

Abstract

Mass drug administration has been implicated as the major cause of drug resistance in nematodes of ruminants. Single-nucleotide polymorphisms (SNPs) at codons 167, 198, and 200 of the beta-tubulin isotype 1 gene are associated with albendazole resistance mechanisms. Although drug resistance is suspected to occur in nematodes of the same order, at present, there is no evidence of a strong correlation between these canonical SNPs and albendazole resistance in hookworms. In the absence of a hookworm strain that is naturally resistant to albendazole, we produced an albendazole-resistant Ancylostoma ceylanicum strain by selective drug pressure. Restriction fragment length polymorphism-PCR (RFLP-PCR) was employed to identify the presence of SNPs previously associated with drug resistance in other nematodes. However, none of the benzimidazole resistance–associated SNPs known in other nematodes were found. A beta-tubulin isotype 1 gene mini-cDNA library was constructed to obtain the complete cDNA gene sequence for the analysis of the entire gene to identify distinct SNPs associated with resistance. Some SNPs were found, but the resulting sequences were not reproducibly detected among the different clones, preventing their association with the resistance mechanism. The parasitological and hematological parameters of the albendazole-resistant strain were characterized and compared to those of the sensitive strain. Although the albendazole-resistant strain was less adapted to its host, with fewer worms recovered, all other parameters analyzed were similar between both strains. The results of the present study indicate that the mechanism of albendazole resistance of the resistant strain described herein must differ from those that have previously been characterized. Thus, new mechanistic studies are needed in the future.

Keywords

Anthelmintic resistance Genetic structure Ancylostoma ceylanicum Beta-tubulin Hookworms 

Notes

Acknowledgements

This work received financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (process number 470968/2014-1), Fundação de Amparo à Pesquisa de Minas Gerais—FAPEMIG (process number APQ-02417-16), and Pró-Reitoria de Pesquisa from Universidade Federal de Minas Gerais (PRPq/UFMG).

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Luis Fernando Viana Furtado
    • 1
  • Pedro Henrique Nascimento de Aguiar
    • 1
  • Luciana Werneck Zuccherato
    • 1
  • Talita Tatiana Guimarães Teixeira
    • 1
  • William Pereira Alves
    • 1
  • Vivian Jordania da Silva
    • 1
  • Robin B Gasser
    • 2
  • Élida Mara Leite Rabelo
    • 1
    Email author
  1. 1.Departamento de Parasitologia, L4 237, Laboratório de Parasitologia MolecularUniversidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Avenida Presidente Antônio Carlos, 6627Belo HorizonteBrazil
  2. 2.Faculty of Veterinary and Agricultural SciencesThe University of MelbourneParkvilleAustralia

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