Pharmacokinetics and pharmacodynamics of antibacterial peptide NZX in Staphylococcus aureus mastitis mouse model

文献类型： 外文期刊

第一作者： Zheng, Xueling

作者： Zheng, Xueling;Yang, Na;Mao, Ruoyu;Hao, Ya;Teng, Da;Wang, Jianhua;Zheng, Xueling;Yang, Na;Mao, Ruoyu;Hao, Ya;Teng, Da;Wang, Jianhua;Zheng, Xueling;Yang, Na;Mao, Ruoyu;Hao, Ya;Teng, Da;Wang, Jianhua

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关键词： Antimicrobial peptide NZX; Staphylococcus aureus; Mechanism of action; Pharmacokinetics; Pharmacodynamics; Mouse mastitis model

期刊名称：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY （ 影响因子：5.0； 五年影响因子：5.2 ）

ISSN： 0175-7598

年卷期： 2024 年 108 卷 1 期

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收录情况： SCI

摘要： Staphylococcus aureus is associated with dairy mastitis, which causes serious economic losses to dairy farming industry. Antibacterial peptide NZX showed good antibacterial activity against S. aureus. This study aimed to evaluate pharmacokinetics and pharmacodynamics of NZX against S. aureus-induced mouse mastitis. NZX exhibited potent in vitro antibacterial activity against the test S. aureus strains (minimal inhibitory concentration (MIC): 0.23-0.46 mu M), low mutant prevention concentration (MPC: 1.18-3.68 mu M), and a long post antibiotic effect (PAE: 2.20-8.84 h), which was superior to those of lincomycin and ceftiofur. Antibacterial mechanisms showed that NZX could penetrate the cell membrane, resulting in obvious cell membrane perforation and morphological changes, and bind to intracellular DNA. Furthermore, NZX had a good stability in milk environment (retention rate: 85.36%, 24 h) than that in mammary homogenate (47.90%, 24 h). In mouse mastitis model, NZX (25-400 mu g/gland) could significantly reduce the bacterial load of mammary tissue in a dose-dependent manner. In addition, NZX (100 mu g/gland) could relieve the inflammatory symptoms of mammary tissue, and significantly decreased its pathological scores. The concentration-time curve of NZX (100 mu g/gland) in the mammary tissue was plotted and the corresponding pharmacokinetic parameters were obtained by non-compartment model calculation. Those parameters of T-max, T-1/2, C-max and AUC were 0.5 h, 35.11 h, 32.49 mu g/g and 391 mu gh/g, respectively. Therefore, these results suggest that NZX could act as a promising candidate for treating dairy mastitis disease caused by S. aureus.

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