Phylogenetic and transcriptomic study of histone deacetylases and histone acetyltransferases in Haemonchus contortus and their inducibility by anthelmintics

As histone-modifying enzymes are key epigenetic regulators of gene expression and contribute to the development of drug resistance in cancer cells, bacteria, and fungal pathogens, they might also participate in anthelmintic resistance in parasitic nematodes. This study presents a comprehensive phylogenetic and transcriptomic analysis of histone deacetylases (HDACs) and histone acetyltransferases (HATs) in Haemonchus contortus , a major gastrointestinal parasite of ruminants. Expression profiles of hdac and hat genes were examined across developmental stages (eggs, L1, L3, exsheathed L3, adult males and females) in a drug-susceptible (ISE) and a benzimidazole-resistant (IRE) strain. Additionally, the inducibility of these genes was assessed following ex vivo exposure of adult worms to sublethal concentrations of albendazole, flubendazole, and ivermectin.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: Lucie Raisová Last name: Stuchlíková. Also, kindly confirm the details in the metadata are correct.Author's first name is Lucie, Raisová and Stuchlíková are both surnames (family name). Other names are correct Most hdac and hat genes exhibited stage-specific level of expression, with the highest levels observed in eggs. Several genes, including hdac2, hdac5, hdac6, hat5, hat9, and hat10 , showed differential expression between the ISE and IRE strains. Notably, hat9 and hat10 were significantly upregulated in resistant worms and were also inducible by anthelmintic exposure in susceptible worms. These findings suggest a potential role for histone-modifying enzymes in the adaptive response to anthelmintic pressure.Affiliations: Journal instruction requires a city for affiliations; however, this is missing in affiliation 1. Please verify if the provided city is correct and amend if necessary.The cities listed in the affiliation are correct. Our faculty is in Hradec Králové, but the university is based in Prague. The data support the hypothesis that histone modifications, mediated by HDACs and HATs, may contribute to the development of anthelmintic resistance in H. contortus . This study provides a foundation for further exploration of epigenetic mechanisms in parasitic nematodes and highlights potential targets for novel control strategies.Graphical abstract is mandatory for publication in this journal. Please provide the graphical abstract.Graphical abstract was uploaded in pdf format.