Mucroporin, the First Cationic Host Defense Peptide from the Venom of Lychas mucronatus
Mucroporin, the First Cationic Host Defense Peptide from the Venom of Lychas mucronatus
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DOI：
10.1128/aac.00542-08
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发表时间：
2008-11-01
影响因子：
4.9
通讯作者：
Li, Wenxin
中科院分区：
文献类型：
--
作者：
Dai, Chao;Ma, Yibao;Li, Wenxin
抗生素的滥用已经把我们的时代带到了危险的边缘，因为耐抗生素病原体的进化速度似乎比抗生素的发明还要快。因此，迫切需要新的药物来治疗细菌感染。阳离子宿主防御肽位于宿主防御系统的第一线，被认为是治疗细菌感染的良好候选者。本文克隆了一种新的阳离子宿主防御肽mucroporin，并对其进行了鉴定。金黄色葡萄球菌的MIC为25 μ g/ml，包括耐药病原菌。以微孔蛋白分子模板为基础，采用氨基酸置换法设计了微孔蛋白- m1。金黄色葡萄球菌的MIC为5 μ g/ml，包括耐甲氧西林金黄色葡萄球菌、耐甲氧西林凝固酶阴性葡萄球菌、耐青霉素金黄色葡萄球菌和耐青霉素表皮葡萄球菌。此外，微孔蛋白m1对革兰氏阴性菌也有抑制作用。微孔蛋白和微孔蛋白- m1的作用方式都是通过破坏细菌的细胞膜而快速杀死细菌，在肽递送后，存活细菌的数量立即减少约4 ~ 5个数量级。这些结果表明，微孔蛋白可以被认为是一种潜在的抗感染药物，特别是用于治疗抗生素耐药病原体。
The misuse of antibiotics has led our age to a dangerous edge, as antibiotic-resistant pathogens appear to evolve more quickly than antibiotics are invented. Thus, new agents to treat bacterial infection are badly needed. Cationic host defense peptides are on the first line of a host defense system and are thought to be good candidates for treating bacterial infection. Here, a novel cationic host defense peptide, mucroporin, was cloned and characterized from the venom of Lychas mucronatus. The MIC for Staphylococcus aureus was 25 mu g/ml, including antibiotic-resistant pathogens. Based on the molecular template of mucroporin, mucroporin-M1 was designed by amino acid substitution. The MIC for S. aureus was 5 mu g/ml, including the antibiotic-resistant pathogens methicillin-resistant S. aureus, methicillin-resistant coagulase-negative Staphylococcus, penicillin-resistant S. aureus, and penicillin-resistant S. epidermidis. Moreover, mucroporin-M1 also inhibited gram-negative bacteria. The modes of action of mucroporin and mucroporin-M1 were both rapid killing by disrupting the cell membrane of bacteria, and the number of surviving bacteria was reduced by about 4 to 5 orders of magnitude immediately after peptide delivery. These results showed that mucroporin could be considered a potential anti-infective drug, especially for treating antibiotic-resistant pathogens.