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蝎毒素肽衍生物的体外和体内抗菌活性及作用机制。

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

机构信息

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, PR China.

出版信息

PLoS One. 2012;7(7):e40135. doi: 10.1371/journal.pone.0040135. Epub 2012 Jul 5.

DOI:10.1371/journal.pone.0040135
PMID:22792229
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3390344/
Abstract

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.

摘要

Kn2-7 是一种从本氏滨蝎毒液中分离得到的抗菌肽（AMP），由我们课题组鉴定。本研究中，Kn2-7 是从 BmKn2 衍生而来，旨在提高抗菌活性和降低溶血活性。Kn2-7 对革兰氏阳性菌和革兰氏阴性菌均表现出增强的抑制活性。此外，Kn2-7 对临床耐药菌株（如耐甲氧西林金黄色葡萄球菌（MRSA））具有更高的抗菌活性。此外，Kn2-7 在金黄色葡萄球菌皮肤感染模型中可有效保护小鼠皮肤免受感染。Kn2-7 通过杀菌机制发挥其抗菌活性。Kn2-7 通过与金黄色葡萄球菌细胞壁中的脂磷壁酸（LTA）和大肠杆菌细胞壁中的脂多糖（LPS）结合，迅速杀死金黄色葡萄球菌和大肠杆菌。最后，与野生型肽 BmKn2 相比，Kn2-7 的溶血活性显著降低。综上所述，Kn2-7 肽可开发为治疗细菌感染的局部治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/aadd18c9cb14/pone.0040135.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/9d92ae4f55a0/pone.0040135.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/801c7ad3a739/pone.0040135.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/0504397d0b7c/pone.0040135.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/c0e431ba5ab4/pone.0040135.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/2ed2716464dd/pone.0040135.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/c4f797d3d927/pone.0040135.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/aadd18c9cb14/pone.0040135.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/9d92ae4f55a0/pone.0040135.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/801c7ad3a739/pone.0040135.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/0504397d0b7c/pone.0040135.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/c0e431ba5ab4/pone.0040135.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/2ed2716464dd/pone.0040135.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/c4f797d3d927/pone.0040135.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bc7/3390344/aadd18c9cb14/pone.0040135.g007.jpg

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