Dataset Information

A Whole Genome Re-Sequencing Based GWA Analysis Reveals Candidate Genes Associated with Ivermectin Resistance in Haemonchus contortus.

ABSTRACT: The most important and broad-spectrum drug used to control the parasitic worms to date is ivermectin (IVM). Resistance against IVM has emerged in parasites, and preserving its efficacy is now becoming a serious issue. The parasitic nematode Haemonchus contortus (Rudolphi, 1803) is economically an important parasite of small ruminants across the globe, which has a successful track record in IVM resistance. There are growing evidences regarding the multigenic nature of IVM resistance, and although some genes have been proposed as candidates of IVM resistance using lower magnification of genome, the genetic basis of IVM resistance still remains poorly resolved. Using the full magnification of genome, we herein applied a population genomics approach to characterize genome-wide signatures of selection among pooled worms from two susceptible and six ivermectin-resistant isolates of H. contortus, and revealed candidate genes under selection in relation to IVM resistance. These candidates also included a previously known IVM-resistance-associated candidate gene HCON_00148840, glc-3. Finally, an RNA-interference-based functional validation assay revealed the HCON_00143950 as IVM-tolerance-associated gene in H. contortus. The possible role of this gene in IVM resistance could be detoxification of xenobiotic in phase I of xenobiotic metabolism. The results of this study further enhance our understanding on the IVM resistance and continue to provide further evidence in favor of multigenic nature of IVM resistance.

SUBMITTER: Khan S

PROVIDER: S-EPMC7230667 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Whole Genome Re-Sequencing Based GWA Analysis Reveals Candidate Genes Associated with Ivermectin Resistance in <i>Haemonchus contortus</i>.

Khan Sawar S Nisar Ayesha A Yuan Jianqi J Luo Xiaoping X Dou Xueqin X Liu Fei F Zhao Xiaochao X Li Junyan J Ahmad Habib H Mehmood Sardar Azhar SA Feng Xingang X

Genes 20200328 4

The most important and broad-spectrum drug used to control the parasitic worms to date is ivermectin (IVM). Resistance against IVM has emerged in parasites, and preserving its efficacy is now becoming a serious issue. The parasitic nematode <i>Haemonchus contortus</i> (Rudolphi, 1803) is economically an important parasite of small ruminants across the globe, which has a successful track record in IVM resistance. There are growing evidences regarding the multigenic nature of IVM resistance, and a ...[more]

PMID: 32231078

Similar Datasets

Project description:Simple Summary Ivermectin (IVM) is a highly effective, broad-spectrum, gold-standard antiparasitic drug that has been used extensively to control nematodes such as Haemonchus contortus. However, IVM-resistant H. contortus populations are now common throughout the world, and there is limited understanding of the mechanisms underlying IVM resistance in H. contortus. Recent studies have offered evidence that the metabolic status of bacteria significantly affects their antibiotic sensitivity and that specific metabolic characteristics are related to resistance. Thus, in the present study, we explored the metabolome of an IVM-resistant H. contortus strain and analyzed the role of metabolism in IVM resistance. These results contribute to our understanding of the mechanisms of IVM resistance in H. contortus. Abstract Resistance to anthelmintics such as ivermectin (IVM) is currently a major problem in the treatment of Haemonchus contortus, an important parasitic nematode of small ruminants. Although many advances have been made in understanding the IVM resistance mechanism, its exact mechanism remains unclear for H. contortus. Therefore, understanding the resistance mechanism becomes increasingly important for controlling haemonchosis. Recent research showed that the metabolic state of bacteria influences their susceptibility to antibiotics. However, little information is available on the roles of metabolites and metabolic pathways in IVM resistance of H. contortus. In this study, comparative analyses of the metabolomics of IVM-susceptible and -resistant adult H. contortus worms were carried out to explore the role of H. contortus metabolism in IVM resistance. In total, 705 metabolites belonging to 42 categories were detected, and 86 differential metabolites (17 upregulated and 69 downregulated) were identified in the IVM-resistant strain compared to the susceptible one. A KEGG pathway analysis showed that these 86 differential metabolites were enriched in 42 pathways that mainly included purine metabolism; the biosynthesis of amino acids; glycine, serine, and threonine metabolism; and cysteine and methionine metabolism. These results showed that amino acid metabolism may be mediated by the uptake of IVM and related with IVM resistance in H. contortus. This study contributes to our understanding of the mechanisms of IVM resistance and may provide effective approaches to manage infection by resistant strains of H. contortus.

Project description:Haemonchus contortus (Hc) is an important parasitic nematode of small ruminants. In this study we assembled the transcriptome of Hc as a model to contribute to the knowledge about the profile of the differential gene expression between two Mexican Hc strains under different anthelmintic resistance statuses, one susceptible and the other resistant to ivermectin (IVMs and IVMr, respectively), in order to improve and/or to have new strategies of control and diagnosis. The transcript sequence reads were assembled and annotated. Overall, ~127 Mbp were assembled and distributed into 77,422 transcript sequences, and 4394 transcripts of the de novo transcriptome were matched base on at least one of the following criteria: (1) Phylum Nemathelminthes and Platyhelminthes, important for animal health care, and (2) ≥55% of sequence identity with other organisms. The gene ontology (GO) enrichment analysis (GOEA) was performed to study the level of gene regulation to IVMr and IVMs strains using Log Fold Change (LFC) filtering values ≥ 1 and ≥ 2. The upregulated-displayed genes obtained via GOEA were: 1993 (for LFC ≥ 1) and 1241 (for LFC ≥ 2) in IVMr and 1929 (for LFC ≥ 1) and 835 (for LFC ≥ 2) in IVMs. The enriched GO terms upregulated per category identified the intracellular structure, intracellular membrane-bounded organelle and integral component of the cell membrane as some principal cellular components. Meanwhile, efflux transmembrane transporter activity, ABC-type xenobiotic transporter activity and ATPase-coupled transmembrane transporter activity were associated with molecular function. Responses to nematicide activity, pharyngeal pumping and positive regulation of synaptic assembly were classified as biological processes that might be involved in events related to the anthelmintic resistance (AR) and nematode biology. The filtering analysis of both LFC values showed similar genes related to AR. This study deepens our knowledge about the mechanisms behind the processes of H. contortus in order to help in tool production and to facilitate the reduction of AR and promote the development of other control strategies, such as anthelmintic drug targets and vaccines.

Dataset Information

A Whole Genome Re-Sequencing Based GWA Analysis Reveals Candidate Genes Associated with Ivermectin Resistance in Haemonchus contortus.

Publications

A Whole Genome Re-Sequencing Based GWA Analysis Reveals Candidate Genes Associated with Ivermectin Resistance in <i>Haemonchus contortus</i>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets