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Detection of Benzimidazole Resistance-Associated Single-Nucleotide Polymorphisms in the Beta-Tubulin Gene in Trichuris trichiura from Brazilian Populations

Valéria Nayara Gomes Mendes de OliveiraUniversidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil;

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Luciana Werneck ZuccheratoUniversidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil;

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Talita Rodrigues dos SantosUniversidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil;

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Élida Mara Leite RabeloUniversidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil;

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Luis Fernando Viana FurtadoUniversidade Federal de Minas Gerais, Faculdade de Farmácia, Belo Horizonte, Minas Gerais, Brazil

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ABSTRACT.

Preventive chemotherapy is recommended by the WHO as the main strategy for controlling infections caused by nematodes in humans, aiming to eliminate the morbidity associated with these infections. This strategy consists of routine periodic administration of benzimidazoles, among other drugs. Although these drugs decrease the intensity of infections, they have the potential to exert selection pressure for genotypes bearing mutations associated with drug resistance, which may result in the establishment of resistant worm populations. There is evidence in the literature of resistance to these drugs in nematodes that infect humans, including in the species Trichuris trichiura. Single-nucleotide polymorphisms (SNPs) in the beta-tubulin gene located at codons 167, 198, and 200 are associated with the mechanism of resistance to benzimidazoles in nematodes. Here, we standardized a molecular technique based on an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) to analyze codons 167, 198, and 200 of T. trichiura. The ARMS-PCR methodology was successfully established to evaluate the codons of interest. A total of 420 samples of individual eggs were analyzed from populations obtained from five Brazilian states. A mutation in codon 198 was observed at a frequency of 4.8% (20/420), while for the other two codons, no polymorphism was observed. This is the first report of the presence of this mutation in populations of T. trichiura in Brazil. This fact and the emergence of the problem already observed in other species reinforces the need for regular monitoring of SNPs related to benzimidazole resistance using techniques that are highly sensitive and specific.

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Author Notes

Address correspondence to Luis Fernando Viana Furtado, Universidade Federal de Minas Gerais, Faculdade de Farmácia, Avenida Presidente Antônio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, Minas Gerais, Brazil. E-mail: lfvfurtado@gmail.com

Financial support: This work was supported by the Fundação de Amparo à Pesquisa do Estado de Minas Gerais – FAPEMIG (Grant nos. APQ-01289-21 and APQ-02273-21).

Authors’ addresses: Valéria Nayara Gomes Mendes de Oliveira, Luciana Werneck Zuccherato, Talita Rodrigues dos Santos, and Élida Mara Leite Rabelo, Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil, E-mails: nayaragmo@gmail.com, lucianawerneck@yahoo.com.br, talitarodrigues779@gmail.com, and elidam.rabelo@gmail.com. Luis Fernando Viana Furtado, Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil, and Universidade do Estado de Minas Gerais, Unidade Passos, Minas Gerais, Brazil, E-mail: lfvfurtado@gmail.com.

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