Dataset Information

Metabolomic and proteomic differences in susceptible and benzimidazole-resistant adult females and males of Haemonchus contortus

ABSTRACT: Anthelmintic resistance in parasitic nematodes, particularly in Haemonchus contortus, poses a significant threat to livestock health and productivity. Since resistance mechanisms have not yet been fully elucidated, the present study employed metabolomic and proteomic analyses of H. contortus adults (females and males separately) from drug-susceptible (ISE) and benzimidazole-resistant (IRE) strains, with a focus on resistance-specific differences. Using nuclear magnetic resonance (NMR)-based metabolomics and mass spectrometry-based proteomics, significant alterations in metabolic and protein expression profiles associated with resistance were identified. Resistant adults exhibited reduced levels of multiple amino acids and tricarboxylic acid cycle intermediates, alongside elevated levels of trehalose, myo-inositol, NAD+, and glycerophosphocholine, suggesting enhanced stress resistance and altered energy metabolism. Proteomic analysis revealed over 3000 proteins, with substantial sex-related differences. Moderate resistance-related differences in protein expression were observed, indicating adaptive biochemical pathways supporting resistance. While some resistance-associated changes in the metabolome and proteome were observed in both sexes, several were distinctly sex-specific. This finding provides the first evidence of such sex-dependent strategies in H. contortus, reinforcing the notion that anthelmintic resistance is a multifaceted and highly complex phenomenon, with many aspects yet to be fully understood. In addition, certain nematode-specific enzymes upregulated in the IRE strain -such as cysteine synthases and transthyretin-like proteins - might be considered as potential targets for future anthelmintic development.

INSTRUMENT(S):

ORGANISM(S): Haemonchus Contortus (barber Pole Worm)

TISSUE(S): Whole Body

SUBMITTER: Michaela Sadibolova

LAB HEAD: Petra Matouskova

PROVIDER: PXD067321 | Pride | 2026-01-02

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	23-81-Strains_PD30_Intensity.msf	Msf
	HCo_uniprotkb_proteome_UP000025227_2025_02_25.fasta	Fasta
	OvisAries_uniprotkb_proteome_UP000002356_2025_02_25.fasta	Fasta
	Q25070-23-81-26.raw	Raw
	Q25070-23-81-27.raw	Raw

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Publications

Metabolomic and proteomic differences in susceptible and benzimidazole-resistant adult females and males of Haemonchus contortus.

Pelantová Helena H Šadibolová Michaela M Žofka Martin M Matoušková Petra P Luzarowski Marcin M Krátký Josef J Štěrbová Karolína K Kuzma Marek M Vosála Ondřej O Skálová Lenka L

Veterinary research 20251224

Anthelmintic resistance in parasitic nematodes, particularly in Haemonchus contortus, poses a significant threat to livestock health and productivity. Since resistance mechanisms have not yet been fully elucidated, the present study employed metabolomic and proteomic analyses of H. contortus adults (females and males separately) from drug-susceptible (ISE) and benzimidazole-resistant (IRE) strains, with a focus on resistance-specific differences. Using nuclear magnetic resonance (NMR)-based meta ...[more]

PMID: 41437124

Similar Datasets

Project description:Infections and diseases caused by parasitic nematodes have a major adverse impact on the health and productivity of animals and humans worldwide. The control of these parasites often relies heavily on the treatment with commercially available chemical compounds (anthelmintics). However, the excessive or uncontrolled use of these compounds in livestock animals has led to major challenges linked to drug resistance in nematodes. Therefore, there is a need to develop new anthelmintics with novel mechanism(s) of action. Recently, we identified a small molecule, KM08948, with nematocidal activity against the free-living model organism Caenorhabditis elegans. Here, we evaluated KM08948’s potential as an anthelmintic in a structure-activity relationship (SAR) study in C. elegans and in the highly pathogenic, blood-feeding Haemonchus contortus (barber’s pole worm), and explored the compound-target relationship using thermal proteome profiling (TPP). First, we synthesised and tested a series of 25 KM08948 analogues for nematocidal activity in both H. contortus (larvae and adults) and C. elegans (young adults), establishing a preliminary nematocidal pharmacophore for both species. We identified several compounds with marked activity against either H. contortus or C. elegans which had greater efficacy than KM08948, and found a significant divergence in compound bioactivity between these two nematode species. We also identified a KM08948 analogue, 25, that moderately inhibited the motility of adult female H. contortus in vitro. Subsequently, we inferred three H. contortus proteins (HCON_00134350, HCON_00021470 and HCON_00099760) and five C. elegans proteins (F30A10.9, F15B9.8, B0361.6, DNC-4 and UNC-11) that interacted directly with KM08948; however, no conserved protein target was shared between the two nematode species. Future work aims to extend the SAR investigation in these and other parasitic nematode species, and validate individual proteins identified here as targets of KM08948. Overall, the present study describes an evaluation of this anthelmintic candidate and highlights some challenges associated with early anthelmintic discovery.