Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing, 100081, China.
Appl Microbiol Biotechnol. 2021 Oct;105(19):7265-7282. doi: 10.1007/s00253-021-11500-x. Epub 2021 Sep 7.
In the present study, we aimed to investigate the antibacterial activity and mechanisms of plectasin-derived peptide NZ2114 in vitro and its therapeutic effects in vivo on broilers challenged with Clostridium perfringens. In vitro assay showed that NZ2114 had potent (minimal inhibitory concentration, 0.91 μM) and rapid antibacterial activity (99.9% reduction within 2 h), and the dual antibacterial mechanisms (including interfering with the cell membrane and intracellular DNA) against C. perfringens CVCC 2030. In vivo study, NZ2114 tended to increase linearly and quadratically the average daily gain as NZ2114 level increased and was the highest at 20 mg/L. NZ2114 at 10 ~ 40 mg/L dramatically reduced jejunal lesion score. Besides, the levels of IL-6, TNF-α, and IL-1β tended to downregulate linearly and quadratically as the NZ2114 level increased and were all the lowest at the dose of 20 mg/L. NZ2114 significantly upregulated those levels of IgA, IgG, IgM, and sIgA with a linear and quadratic dose effect, with the highest IgA, IgG, IgM, and sIgA at 20 mg/L. Finally, NZ2114 tended to linearly and quadratically increase the numerical value of crypt depth, with the lowest value at 40 mg/L. Lincomycin only dramatically reduced the jejunal lesion score and increased the numerical value of crypt depth. These results indicate that NZ2114 has the potential as a new alternative to antibiotics for the treatment of C. perfringens-induced necrotic enteritis infection.Key points• NZ2114 could kill C. perfringens by dual antibacterial mechanisms• Broiler necrotic enteritis model induced by C. perfringens was established• NZ2114 treatment could ameliorate C. perfringens-induced necrotic enteritis.
在本研究中，我们旨在研究 plectasin 衍生肽 NZ2114 的体外抗菌活性和机制及其在感染产气荚膜梭菌的肉鸡体内的治疗效果。体外试验表明，NZ2114 具有强大的（最小抑菌浓度，0.91μM）和快速的抗菌活性（2 小时内减少 99.9%），对产气荚膜梭菌 CVCC 2030 具有双重抗菌机制（包括干扰细胞膜和细胞内 DNA）。体内研究表明，随着 NZ2114 水平的增加，NZ2114 呈线性和二次增加平均日增重，并在 20mg/L 时最高。NZ2114 在 10 至 40mg/L 时显著降低空肠病变评分。此外，随着 NZ2114 水平的增加，IL-6、TNF-α 和 IL-1β 的水平呈线性和二次下调趋势，在 20mg/L 时均最低。NZ2114 显著上调了 IgA、IgG、IgM 和 sIgA 的水平，具有线性和二次剂量效应，在 20mg/L 时达到最高。最后，NZ2114 呈线性和二次增加隐窝深度的数值，在 40mg/L 时达到最低。林可霉素仅显著降低空肠病变评分和增加隐窝深度的数值。这些结果表明，NZ2114 有潜力作为抗生素治疗产气荚膜梭菌诱导的坏死性肠炎感染的替代品。
NZ2114 可以通过双重抗菌机制杀死产气荚膜梭菌。
建立了由产气荚膜梭菌引起的肉鸡坏死性肠炎模型。
NZ2114 治疗可改善产气荚膜梭菌诱导的坏死性肠炎。
