计算机辅助设计开发高特异性抑制沙门氏菌的新型嵌合细胞裂解酶

In Silico Development of Novel Chimeric Lysins with Highly Specific Inhibition against Salmonella by Computer-Aided Design

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中文摘要:通过生物信息学分析和电子设计,获得了四种由沙门氏菌噬菌体细胞裂解酶和新型抗菌肽LeuA-P融合形成的新型嵌合细胞裂解酶(P361、P362、P371和P372)。重组嵌合细胞裂解酶在大肠杆菌BL21(DE3)中表达,并对沙门氏菌具有很强的抑制作用。P362和P372对伤寒杆菌CMCC 50071的最低抑菌浓度(MICs)分别为8和16μg/mL。1倍MIC的P362和P372均可增加外膜通透性、裂解细胞壁肽聚糖、使胞内核酸和蛋白泄漏,最终有效杀死沙门氏菌而不产生耐药性。P362、P372和山梨酸钾联合使用可使受污染的冷鲜鸡肉中微生物数量减少3 logCUF/g以上,并将保质期延长7天。抗菌肽(AMP)-细胞裂解酶嵌合体处理使得噬菌体细胞裂解酶在体外无法特异性抑制外膜致密的革兰氏阴性菌。
外文摘要:Four novel chimeric lysins (P361, P362, P371, and P372), which were the fusion of Salmonella phage lysins and novel antimicrobial peptide LeuA-P, were obtained using bioinformatics analysis and in silico design. The recombinant chimeric lysins were expressed in E. coli BL21(DE3) strain and showed highly specific inhibition against Salmonella. The minimal inhibitory concentrations (MICs) of P362 and P372 to S. typhi CMCC 50071 were 8 and 16 mu g/mL, respectively. Both 1 x MIC P362 and P372 could increase the outer membrane permeability and cleave the cell wall peptidoglycan, causing the leakage of intracellular nucleic acids and proteins and ultimately killing Salmonella efficiently without drug resistance. The combination of P362, P372, and potassium sorbate reduced more than 3 log CFU/g counts of microorganisms in contaminated chilled chicken and extended the shelf life by 7 days. The strategy of antimicrobial peptide (AMP)-lysin chimera inspired the inability of phage lysin to specifically inhibit Gram-negative bacteria with dense outer membranes in vitro.
外文关键词:Salmonella;antimicrobial peptide;chimeric lysins;in silico design;outer membrane;peptidoglycan
作者:Nie, T;Meng, FQ;Zhou, LB;Lu, FX;Bie, XM;Lu, ZX;Lu, YJ
作者单位:Nanjing Agr Univ;Nanjing Univ Finance & Econ
期刊名称:JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
期刊影响因子:4.192
出版年份:2021
出版刊次:12
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  1. 编译服务:噬菌体
  2. 编译者:虞德容
  3. 编译时间:2021-05-06