Abstract

BackgroundEimeria tenella is a highly pathogenic coccidian that causes avian coccidiosis. Both nitromezuril (NZL) and ethanamizuril (EZL) are novel triazine compounds with high anticoccidial activity, but the mechanisms of their action are still unclear. This study explored the response of E. tenella to NZL and EZL by the study of changes in protein composition of the second-generation merozoites.MethodsLabel-free quantification (LFQ) proteomics of the second-generation merozoites of E. tenella following NZL and EZL treatment were studied by LC-MS/MS to explore the mechanisms of action. The identified proteins were annotated and analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) networks analysis.ResultsA total of 1430 proteins were identified by LC-MS/MS, of which 375 were considered as differential proteins in response to drug treatment (DPs). There were 26 only found in the NZL treatment group (N-group), 63 exclusive to the EZL treatment group (E-group), and 80 proteins were present in both drug groups. In addition, among the DPs, the abundant proteins with significantly altered expression in response to drug treatment (SDPs) were found compared with the C-group, of which 49 were upregulated and 51 were downregulated in the N-group, and 66 upregulated and 79 downregulated in the E-group. Many upregulated proteins after drug treatment were involved in transcription and protein metabolism, and surface antigen proteins (SAGs) were among the largest proportion of the downregulated SDPs. Results showed the top two enriched GO terms and the top one enriched pathway treated with EZL and NZL were related, which indicated that these two compounds had similar modes of action.ConclusionsLFQ proteomic analysis is a feasible method for screening drug-related proteins. Drug treatment affected transcription and protein metabolism, and SAGs were also affected significantly. This study provided new insights into the effects of triazine anticoccidials against E. tenella.

Highlights

  • Eimeria tenella is a highly pathogenic coccidian that causes avian coccidiosis

  • A total of 1430 proteins of the second-generation merozoites of E. tenella were identified in three groups

  • There were 21 and 20 downregulated differential proteins in response to drug treatment (DPs) belonging to surface antigen proteins (SAGs) family members in the NZL treatment group (N-group) and EZL treatment group (E-group), respectively, including SAG13 (UniProt: Q70CD1), SAG21 (UniProt: Q70CC8), SAG4 (UniProt: Q70CD9), SAG18 (UniProt: Q70CC6), SAG family member (UniProt: U6L233), which were shared by two groups

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Summary

Introduction

Eimeria tenella is a highly pathogenic coccidian that causes avian coccidiosis. Both nitromezuril (NZL) and ethanamizuril (EZL) are novel triazine compounds with high anticoccidial activity, but the mechanisms of their action are still unclear. This study explored the response of E. tenella to NZL and EZL by the study of changes in protein composition of the second-generation merozoites. Coccidiosis is a serious intestinal disease caused by Eimeria (Apicomplexa: Eimeriidae) with strict host specificity and results in huge economic losses in the global poultry industry every year [1, 2]. Eimeria tenella is considered to be a highly pathogenic and prevalent, and was selected as the candidate for study. It is probably a wise choice to study the changes of the second-generation merozoites after drug treatment

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