Cargando…

Comparative Metabolome Analyses of Ivermectin-Resistant and -Susceptible Strains of Haemonchus contortus

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 underst...

Descripción completa

Detalles Bibliográficos
Autores principales: Tuersong, Waresi, Liu, Xin, Wang, Yifan, Wu, Simin, Qin, Peixi, Zhu, Shengnang, Liu, Feng, Wang, Chunqun, Hu, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913829/
https://www.ncbi.nlm.nih.gov/pubmed/36766346
http://dx.doi.org/10.3390/ani13030456
_version_ 1784885522705940480
author Tuersong, Waresi
Liu, Xin
Wang, Yifan
Wu, Simin
Qin, Peixi
Zhu, Shengnang
Liu, Feng
Wang, Chunqun
Hu, Min
author_facet Tuersong, Waresi
Liu, Xin
Wang, Yifan
Wu, Simin
Qin, Peixi
Zhu, Shengnang
Liu, Feng
Wang, Chunqun
Hu, Min
author_sort Tuersong, Waresi
collection PubMed
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.
format Online
Article
Text
id pubmed-9913829
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-99138292023-02-11 Comparative Metabolome Analyses of Ivermectin-Resistant and -Susceptible Strains of Haemonchus contortus Tuersong, Waresi Liu, Xin Wang, Yifan Wu, Simin Qin, Peixi Zhu, Shengnang Liu, Feng Wang, Chunqun Hu, Min Animals (Basel) Article 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. MDPI 2023-01-28 /pmc/articles/PMC9913829/ /pubmed/36766346 http://dx.doi.org/10.3390/ani13030456 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tuersong, Waresi
Liu, Xin
Wang, Yifan
Wu, Simin
Qin, Peixi
Zhu, Shengnang
Liu, Feng
Wang, Chunqun
Hu, Min
Comparative Metabolome Analyses of Ivermectin-Resistant and -Susceptible Strains of Haemonchus contortus
title Comparative Metabolome Analyses of Ivermectin-Resistant and -Susceptible Strains of Haemonchus contortus
title_full Comparative Metabolome Analyses of Ivermectin-Resistant and -Susceptible Strains of Haemonchus contortus
title_fullStr Comparative Metabolome Analyses of Ivermectin-Resistant and -Susceptible Strains of Haemonchus contortus
title_full_unstemmed Comparative Metabolome Analyses of Ivermectin-Resistant and -Susceptible Strains of Haemonchus contortus
title_short Comparative Metabolome Analyses of Ivermectin-Resistant and -Susceptible Strains of Haemonchus contortus
title_sort comparative metabolome analyses of ivermectin-resistant and -susceptible strains of haemonchus contortus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913829/
https://www.ncbi.nlm.nih.gov/pubmed/36766346
http://dx.doi.org/10.3390/ani13030456
work_keys_str_mv AT tuersongwaresi comparativemetabolomeanalysesofivermectinresistantandsusceptiblestrainsofhaemonchuscontortus
AT liuxin comparativemetabolomeanalysesofivermectinresistantandsusceptiblestrainsofhaemonchuscontortus
AT wangyifan comparativemetabolomeanalysesofivermectinresistantandsusceptiblestrainsofhaemonchuscontortus
AT wusimin comparativemetabolomeanalysesofivermectinresistantandsusceptiblestrainsofhaemonchuscontortus
AT qinpeixi comparativemetabolomeanalysesofivermectinresistantandsusceptiblestrainsofhaemonchuscontortus
AT zhushengnang comparativemetabolomeanalysesofivermectinresistantandsusceptiblestrainsofhaemonchuscontortus
AT liufeng comparativemetabolomeanalysesofivermectinresistantandsusceptiblestrainsofhaemonchuscontortus
AT wangchunqun comparativemetabolomeanalysesofivermectinresistantandsusceptiblestrainsofhaemonchuscontortus
AT humin comparativemetabolomeanalysesofivermectinresistantandsusceptiblestrainsofhaemonchuscontortus