Expression and characterization of the new antimicrobial peptide AP138L-arg26 anti Staphylococcus aureus

文献类型： 外文期刊

第一作者： Zhang, Kun

作者： Zhang, Kun;Yang, Na;Teng, Da;Mao, Ruoyu;Hao, Ya;Wang, Jianhua;Zhang, Kun;Yang, Na;Teng, Da;Mao, Ruoyu;Hao, Ya;Wang, Jianhua;Zhang, Kun;Yang, Na;Teng, Da;Mao, Ruoyu;Hao, Ya;Wang, Jianhua

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关键词： AP138L-arg26; Staphylococcus aureus; Recombination expression; Safety; Bactericidal mechanism

期刊名称：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY （ 影响因子：4.3； 五年影响因子：5.1 ）

ISSN： 0175-7598

年卷期： 2024 年 108 卷 1 期

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收录情况： SCI

摘要： The low activity and yield of antimicrobial peptides (AMPs) are pressing problems. The improvement of activity and yield through modification and heterologous expression, a potential way to solve the problem, is a research hot-pot. In this work, a new plectasin-derived variant L-type AP138 (AP138L-arg26) was constructed for the study of recombination expression and druggablity. As a result, the total protein concentration of AP138L-arg26 was 3.1 mg/mL in Pichia pastoris X-33 supernatant after 5 days of induction expression in a 5-L fermenter. The recombinant peptide AP138L-arg26 has potential antibacterial activity against selected standard and clinical Gram-positive bacteria (G(+), minimum inhibitory concentration (MIC) 2-16 mu g/mL) and high stability under different conditions (temperature, pH, ion concentration) and 2xMIC of AP138L-arg26 could rapidly kill Staphylococcus aureus (S. aureus) (>99.99%) within 1.5 h. It showed a high safety in vivo and in vivo and a long post-antibiotic effect (PAE, 1.91 h) compared with vancomycin (1.2 h). Furthermore, the bactericidal mechanism was revealed from two dimensions related to its disruption of the cell membrane resulting in intracellular potassium leakage (2.5-fold higher than control), and an increase in intracellular adenosine triphosphate (ATP), and reactive oxygen species (ROS), the decrease of lactate dehydrogenase (LDH) and further intervening metabolism in S. aureus. These results indicate that AP138L-arg26 as a new peptide candidate could be used for more in-depth development in the future.

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