Molecular Study of Benzimidazole Resistance in  Teladorsagia circumcincta  Isolated from Sheep in North of Iran

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Abstract

Background:

Resistance to benzimidazole (BZ) compounds is common in Teladorsagia circumcincta populations in sheep and goats worldwide. Given the importance of anthelmintic resistance and shortage of information on single nucleotide polymorphisms (SNPs) in this prevalent nematode in Iran, this study was conducted.

Methods:

From June to September 2016, abomasa of 139 sheep of different sexes and ages in Amol City slaughterhouse, northern Iran were examined for isolation of nematodes. Totally 45 male T. circumcincta confirmed by both microscopical and nested-PCR-RFLP methods were included in this study. Susceptibility or resistance of each single T. circumcincta worm to benzimidazoles was assessed using allele-specific PCR.

Results:

Frequency of genotypes in the present study were 33.33% heterozygote BZ and 66.67% BZ homozygote sensitive. No homozygote resistant worm was found.

Conclusion:

Resistance against BZs in T. circumcincta of sheep has occurred at a low prevalence in the north of Iran. However, mutated genes might get dominant under drug selection in future. Hence, periodic investigations for early detection of mutated alleles in nematode populations using accurate and sensitive molecular methods such as PCR-RFLP is recommended.

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Most cited references 35

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An inconvenient truth: global worming and anthelmintic resistance.

Ray Kaplan, Anand N Vidyashankar (2012)

Over the past 10-15 years, we have witnessed a rapid increase in both the prevalence and magnitude of anthelmintic resistance, and this increase appears to be a worldwide phenomenon. Reports of anthelmintic resistance to multiple drugs in individual parasite species, and in multiple parasite species across virtually all livestock hosts, are increasingly common. In addition, since the introduction of ivermectin in 1981, no novel anthelmintic classes were developed and introduced for use in livestock until recently with the launch of monepantel in New Zealand. Thus, livestock producers are often left with few options for effective treatment against many important parasite species. While new anthelmintic classes with novel mechanisms of action could potentially solve this problem, new drugs are extremely expensive to develop, and can be expected to be more expensive than older drugs. Thus, it seems clear that the "Global Worming" approach that has taken hold over the past 40-50 years must change, and livestock producers must develop a new vision for parasite control and sustainability of production. Furthermore, parasitologists must improve methods for study design and data analysis that are used for diagnosing anthelmintic resistance, especially for the fecal egg count reduction test (FECRT). Currently, standards for diagnosis of anthelmintic resistance using FECRT exist only for sheep. Lack of standards in horses and cattle and arbitrarily defined cutoffs for defining resistance, combined with inadequate analysis of the data, mean that errors in assigning resistance status are common. Similarly, the lack of standards makes it difficult to compare data among different studies. This problem needs to be addressed, because as new drugs are introduced now and in the future, the lack of alternative treatments will make early and accurate diagnosis of anthelmintic resistance increasingly important. Copyright © 2011 Elsevier B.V. All rights reserved.

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A new class of anthelmintics effective against drug-resistant nematodes.

S. W. Weber, R Clover, P. Ducray … (2008)

Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics--the benzimidazoles, imidazothiazoles and macrocyclic lactones--has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.

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Phenotyping and genotyping of Haemonchus contortus isolates reveals a new putative candidate mutation for benzimidazole resistance in nematodes.

Marc Ghisi, Ronald Kaminsky, Pascal Mäser (2007)

In order to monitor and eventually control the spread of drug-resistant Haemonchus contortus, knowledge of the molecular mechanisms underlying resistance is essential. Here we phenotypically and genotypically characterize three multidrug-resistant H. contortus field isolates from Australia and South Africa. All were significantly less susceptible to thiabendazole than a sensitive reference strain in an in vitro egg-hatch assay. The sensitivity was further reduced in a surviving population after treatment of infected sheep with albendazole. The beta-tubulin genes were amplified from genomic DNA of the H. contortus isolates, cloned, and sequenced. There was a high degree of sequence variation. The known mutation phenylalanine-200 to tyrosine (F200Y) occurred in 60% of the sequences from resistant isolates, but not in the sensitive reference. Interestingly, 90% of the beta-tubulin sequences from resistant isolates lacking tyrosine-200 carried another mutation nearby, glutamate-198 to alanine (E198A). This mutation was not found in the sensitive isolate, nor in sequences from resistant isolates carrying the mutation F200Y. However, the mutation E198A is known from benomyl-resistant isolates of phytopathogenic fungi such as Monilinia fructicola. The finding that alanine-198 correlates with thiabendazole resistance in H. contortus isolates from South Africa and Australia suggests that also in nematodes, the mutation E198A plays a role in benzimidazole resistance. Alanine-198 alleles of beta-tubulin can be detected by PCR-RFLP and we suggest to include this test in future surveys of H. contortus field populations.

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Author and article information

Journal

Journal ID (nlm-ta): Iran J Parasitol

Journal ID (iso-abbrev): Iran J Parasitol

Journal ID (publisher-id): IJPA

Journal ID (pmc): IJPA

Title: Iranian Journal of Parasitology

Publisher: Tehran University of Medical Sciences

ISSN (Print): 1735-7020

ISSN (Electronic): 2008-238X

Publication date (Print): Oct-Dec 2019

Volume: 14

Issue: 4

Pages: 646-651

Affiliations

[1. ] Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran

[2. ] Department of Clinical Sciences, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran

Author notes

[* ] Correspondence Email: aliasghar.bahari@ 123456basu.ac.ir

Article

Publisher ID: IJPA-14-646

DOI: 10.18502/ijpa.v14i4.2108

PMC ID: 7028222

PubMed ID: 32099568

SO-VID: f3144baa-52fd-4c95-bb2d-530a85cc551f

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Study of Benzimidazole Resistance in Teladorsagia circumcincta Isolated from Sheep in North of Iran

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Abstract

Background:

Methods:

Results:

Conclusion:

Related collections

Malaria vaccine development

Most cited references 35

An inconvenient truth: global worming and anthelmintic resistance.

A new class of anthelmintics effective against drug-resistant nematodes.

Phenotyping and genotyping of Haemonchus contortus isolates reveals a new putative candidate mutation for benzimidazole resistance in nematodes.

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