In vitro and in vivo characterization of a new recombinant antimicrobial peptide, MP1102, against methicillin-resistant Staphylococcus aureus

文献类型： 外文期刊

第一作者： Zhang, Yong

作者： Zhang, Yong;Teng, Da;Wang, Xiumin;Mao, Ruoyu;Cao, Xintao;Hu, Xiaoyuan;Zong, Lifen;Wang, Jianhua;Zhang, Yong;Teng, Da;Wang, Xiumin;Mao, Ruoyu;Cao, Xintao;Hu, Xiaoyuan;Zong, Lifen;Wang, Jianhua

作者机构：

关键词： Molecular design;MP1102;Pichia pastoris;MRSA;Antimicrobial peptides

期刊名称：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY （ 影响因子：4.813； 五年影响因子：4.697 ）

ISSN：

年卷期：

页码：

收录情况： SCI

摘要： Currently, more antimicrobial drug candidates are urgently needed to combat the rise in drug-resistance among pathogenic microbes. A new antimicrobial peptide, MP1102, a variant of NZ2114, was designed, evaluated, and overexpressed in Pichia pastoris. The total secreted protein in cultures reached 695 mg/l, and the concentration of the recombinant MP1102 (rMP1102) was 292 mg/l. rMP1102 was purified from the fermentation supernatant by one-step cation exchange chromatography to obtain a yield of 197.1 mg/l with 96.4 % purity. rMP1102 exhibited potent activity against Gram-positive bacteria, and its minimum inhibitory concentrations (MICs) for four Staphyloccocus aureus (S. aureus) strains ranged from 0.028 to 0.11 mu M, and it had stronger activity (MIC = 0.04 to 0.23 mu M) to 20 clinical isolates of MRSA (cMRSA) than rNZ2114 (MIC = 0.11 to 0.90 mu M). rMP1102 was shown to kill over 99.9 % of tested S. aureus cells within 6 h when treated at one, two, and four times its MIC and over 90 % of S. aureus cells within 12 h at concentrations of 5, 10, and 20 mg/kg in a mouse thigh infection model. The higher sensitivity of MRSA to MP1102 than to its parental peptide, NZ2114, indicated by this initial pharmacodynamic analysis suggests a possible difference in the killing mechanism of these two molecules. rMP1102 caused less than 0.05 % hemolytic activity at 128 mu g/ml and exhibited good thermostability from 20 to 80 A degrees C, with its highest activity being observed at pH 8.0. These results suggest that this yeast expression system is feasible for large-scale production, and rMP1102 exerted stronger activity against S. aureus than NZ2114 via a different mechanism and exhibited potential as a new antimicrobial agent for S. aureus, especially MRSA infections.

分类号： Q939.9`Q81

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