Profile of lysine acetylation in Eimeria tenella and its potential implications for anticoccidial research
摘要
Coccidiosis has resulted in substantial economic losses in the poultry industry. The prevalence and severity of drug resistance to anticoccidial agents have exacerbated the challenges associated with controlling coccidiosis. Consequently, exploring novel drug targets is crucial for the prevention and treatment of coccidiosis.
MethodsIn this study, we performed acetylation modification proteomics on the sporozoites and merozoites of Eimeria tenella during the asexual stage. Moreover, the anticoccidial efficacy of histone deacetylase (HDAC) inhibitors was evaluated both in vitro and in vivo.
ResultsIn total, 341 differentially acetylated proteins and 558 differentially acetylated modification sites were identified. Histones H2A, H2B, H2B variants, H3, and H4 are all acetylated and have multiple acetylation sites, suggesting that acetylation plays important roles in the gene regulation, replication, and development of E. tenella. KEGG pathway analysis revealed that glycolysis/gluconeogenesis pathway was enriched. Glycolysis is the main mode of energy metabolism in Apicomplexa. In the glycolysis pathway, eight key enzymes are downregulated by acetylation and have multiple acetylation sites. It has been suggested that histone deacetylase (HDAC) is the target of anticoccidial action. Trichostatin A (TSA, an inhibitor of HDAC family deacetylases) and nicotinamide (NAM, an inhibitor of SIRT family deacetylases) can inhibit sporozoite invasion (P ≤ 0.01) and promote sporozoite apoptosis (P ≤ 0.05). Intraperitoneal injection of TSA and NAM can reduce chicken caecal lesions and oocyst shedding, and the anticoccidial index can reach 143.
ConclusionsThis study is the first to investigate the anticoccidial effect of deacetylase inhibitors, providing a new strategy for the prevention and control of coccidiosis.
Graphical Abstract