Key Laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture and Rural Affairs/Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Minhang District, Shanghai, 200241, China.
Parasit Vectors. 2022 Sep 8;15(1):319. doi: 10.1186/s13071-022-05412-6.
Avian coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The extensive use of anticoccidial drugs has resulted in an increase in drug resistance. Ethanamizuril (EZL) is a novel triazine with high anticoccidial activity.
We compared oocyst production and sporulation between EZL-sensitive (S) and EZL-resistant Eimeria tenella strains (R10 and R200) and used label-free quantitative proteomics to identify differentially expressed proteins (DEPs) between these strains.
We generated two EZL-resistant E. tenella strains: strain R10, which was induced using a constant dose of 10 mg EZL/kg poultry feed, and strain R200, which was generated by gradually increasing the EZL dosage to 200 mg EZL/kg poultry feed. With an increase in resistance, the total oocyst output decreased, but the percentage of sporulation did not change significantly. We identified a total of 7511 peptides and 1282 proteins, and found 152 DEPs in the R10 strain versus the S strain, 426 DEPs in the R200 strain versus the S strain and 494 DEPs in the R200 strain versus the R10 strain. When compared with the S strain, 86 DEPs were found to have consistent trends in both resistant strains. The DEPs were primarily involved in ATP and GTP binding, invasion, and membrane components. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the DEPs suggested that they are involved in transcription and translation processes. Protein-protein interaction network analysis of the 86 DEPs showed that 10 proteins were hubs in the functional interaction network (≥ 8 edges) and five of them were ribosomal proteins.
The results of the present study indicate that the resistance mechanisms of E. tenella against EZL might be related to the transcriptional and translational processes, especially in the factors that inhibit the growth of parasites. The DEPs found in this study provide new insights into the resistance mechanisms of E. tenella against EZL. Further research on these potential targets holds promise for new chemotherapeutic approaches for controlling E. tenella infections.
禽类球虫病是一种重要的寄生虫病，对全球家禽业有严重的不良影响。抗球虫药物的广泛使用导致了药物耐药性的增加。乙酰胺嗪（EZL）是一种具有高抗球虫活性的新型三嗪。
我们比较了 EZL 敏感（S）和 EZL 耐药艾美耳球虫（R10 和 R200）的卵囊产量和孢子化，并使用无标记定量蛋白质组学技术鉴定这些菌株之间差异表达的蛋白质（DEPs）。
我们生成了两个 EZL 耐药的柔嫩艾美耳球虫株：用 10mg EZL/kg 禽饲料的恒定剂量诱导的 R10 株，以及用逐渐增加至 200mg EZL/kg 禽饲料的剂量诱导的 R200 株。随着耐药性的增加，总卵囊产量减少，但孢子化的百分比没有明显变化。我们鉴定了总共 7511 个肽段和 1282 个蛋白质，在 R10 株与 S 株之间发现了 152 个 DEPs，在 R200 株与 S 株之间发现了 426 个 DEPs，在 R200 株与 R10 株之间发现了 494 个 DEPs。与 S 株相比，在两个耐药株中发现了 86 个具有一致趋势的 DEPs。这些 DEPs主要参与 ATP 和 GTP 结合、入侵和膜成分。DEPs 的基因本体论和京都基因与基因组百科全书途径分析表明，它们参与转录和翻译过程。86 个 DEPs 的蛋白质-蛋白质相互作用网络分析表明，10 个蛋白质是功能相互作用网络中的枢纽（≥8 个边缘），其中 5 个是核糖体蛋白。
本研究结果表明，柔嫩艾美耳球虫对 EZL 的耐药机制可能与转录和翻译过程有关，特别是在抑制寄生虫生长的因素方面。本研究中发现的 DEPs 为柔嫩艾美耳球虫对 EZL 的耐药机制提供了新的见解。对这些潜在靶标的进一步研究有望为控制柔嫩艾美耳球虫感染提供新的化疗方法。
