Multi-Omic Profiling, Structural Characterization, and Potent Inhibitor Screening of Evasion-Related Proteins of a Parasitic Nematode, Haemonchus contortus , Surviving Vaccine Treatment.
Nikola PalevichPaul H MacleanVincenzo CarboneRuy JaureguiSaleh UmairPublished in: Biomedicines (2023)
The emergence of drug-resistant parasitic nematodes in both humans and livestock calls for development of alternative and cost-effective control strategies. Barbervax ® is the only registered vaccine for the economically important ruminant strongylid Haemonchus contortus . In this study, we compared the microbiome, genome-wide diversity, and transcriptome of H. contortus adult male populations that survived vaccination with an experimental vaccine after inoculation in sheep. Our genome-wide SNP analysis revealed 16 putative candidate vaccine evasion genes. However, we did not identify any evidence for changes in microbial community profiling based on the 16S rRNA gene sequencing results of the vaccine-surviving parasite populations. A total of fifty-eight genes were identified as significantly differentially expressed, with six genes being long non-coding (lnc) RNAs and none being putative candidate SNP-associated genes. The genes that highly upregulated in surviving parasites from vaccinated animals were associated with GO terms belonging to predominantly molecular functions and a few biological processes that may have facilitated evasion or potentially lessened the effect of the vaccine. These included five targets: astacin (ASTL), carbonate dehydratase (CA2), phospholipase A2 (PLA2), glutamine synthetase (GLUL), and fatty acid-binding protein (FABP3). Our tertiary structure predictions and modelling analyses were used to perform in silico searches of all published and commercially available inhibitor molecules or substrate analogs with potential broad-spectrum efficacy against nematodes of human and veterinary importance.
Keyphrases
- genome wide
- dna methylation
- drug resistant
- microbial community
- copy number
- single cell
- binding protein
- genome wide identification
- multidrug resistant
- fatty acid
- endothelial cells
- gene expression
- molecular docking
- systematic review
- cystic fibrosis
- pseudomonas aeruginosa
- transcription factor
- single molecule
- plasmodium falciparum
- rna seq
- genome wide analysis
- combination therapy