Antibacterial activity and mechanism of a scorpion venom peptide derivative in vitro and in vivo.

Antibacterial activity and mechanism of a scorpion venom peptide derivative in vitro and in vivo.
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DOI:
10.1371/journal.pone.0040135
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Li W
Li W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cao L;Dai C;Li Z;Fan Z;Song Y;Wu Y;Cao Z;Li W

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BmKn 2是本课题组从东亚钳蝎(Mesobuthus martensii Karsch)毒中分离得到的一种抗菌肽(AMP)。本研究从BmKn 2中衍生Kn 2 -7,以提高抗菌活性和降低溶血活性。Kn 2 -7对革兰氏阳性菌和革兰氏阴性菌均表现出较强的抑制活性。此外,Kn 2 -7对临床耐药菌株如耐甲氧西林金黄色葡萄球菌(MRSA)表现出较高的抗菌活性。此外,局部使用Kn 2 -7有效地保护小鼠皮肤免受S.金黄色葡萄球菌小鼠皮肤感染模型。kn 2 -7通过杀菌机制发挥其抗菌活性。Kn 2 -7杀死S. aureus和E.大肠杆菌中的脂磷壁酸(LTA)。aureus细胞壁和E. coli细胞壁。最后,与野生型肽BmKn 2相比,Kn 2 -7的溶血活性显著降低。综上所述,Kn 2 -7肽可以被开发为用于治疗细菌感染的局部治疗剂。
BmKn2 is an antimicrobial peptide (AMP) characterized from the venom of scorpion Mesobuthus martensii Karsch by our group. In this study, Kn2-7 was derived from BmKn2 to improve the antibacterial activity and decrease hemolytic activity. Kn2-7 showed increased inhibitory activity against both Gram-positive bacteria and Gram-negative bacteria. Moreover, Kn2-7 exhibited higher antibacterial activity against clinical antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA). In addition, the topical use of Kn2-7 effectively protected the skin of mice from infection in an S. aureus mouse skin infection model. Kn2-7 exerted its antibacterial activity via a bactericidal mechanism. Kn2-7 killed S. aureus and E. coli rapidly by binding to the lipoteichoic acid (LTA) in the S. aureus cell wall and the lipopolysaccharides (LPS) in the E. coli cell wall, respectively. Finally, the hemolytic activity of Kn2-7 was significantly decreased, compared to the wild-type peptide BmKn2. Taken together, the Kn2-7 peptide can be developed as a topical therapeutic agent for treating bacterial infections.
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