Antibacterial mechanism and structure-activity relationships of Bombyx mori cecropin A

文献类型： 外文期刊

第一作者： Tian, Yuyuan

作者： Tian, Yuyuan;Tian, Yuyuan;Tian, Yuyuan;Wei, Hongxian;Lu, Fuping;Wu, Huazhou;Lou, Dezhao;Wang, Shuchang;Geng, Tao

作者机构：

关键词： antimicrobial peptide; cecropin A; cell membrane; DNA degradation; structure-activity optimization

期刊名称：INSECT MOLECULAR BIOLOGY （ 影响因子：2.3； 五年影响因子：2.8 ）

ISSN： 0962-1075

年卷期： 2024 年

页码：

收录情况： SCI

摘要： Bombyx mori cecropin A (Bmcecropin A) has antibacterial, antiviral, anti-filamentous fungal and tumour cell inhibition activities and is considered a potential succedaneum for antibiotics. We clarified the antibacterial mechanism and structure-activity relationships and then directed the structure-activity optimization of Bmcecropin A. Firstly, we found Bmcecropin A shows a strong binding force and permeability to cell membranes like a detergent; Bmcecropin A could competitively bind to the cell membrane with the cell membrane-specific dye DiI, then damaged the membrane for the access of DiI into the cytoplasm and leading to the leakage of electrolyte and proteins. Secondly, we found Bmcopropin A could also bind to and degrade DNA; furthermore, DNA library polymerase chain reaction (PCR) results indicated that Bmcecropin A inhibited DNA replication by non-specific binding. In addition, we have identified C-terminus amidation and serine-lysine- glycine (SLG) amino acids of Bmcecropin A played critical roles in the membrane damage and DNA degradation. Based on the above results, we designed a mutant of Bmcecropin A (E-9 to H, D-17 to K, K-33 to A), which showed higher antibacterial activity, thermostability and pH stability than ampicillin but no haemolytic activity. Finally, we speculated that Bmcecropin A damaged the cell membrane through a carpet model and drew the schematic diagram of its antibacterial mechanism, based on the antibacterial mechanism and the three-dimensional configuration. These findings yield insights into the mechanism of antimicrobial peptide-pathogen interaction and beneficial for the development of new antibiotics.

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