Dai Chao, Ma Yibao, Zhao Zhenhuan, Zhao Ruiming, Wang Qian, Wu Yingliang, Cao Zhijian, Li Wenxin
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China.
Antimicrob Agents Chemother. 2008 Nov;52(11):3967-72. doi: 10.1128/AAC.00542-08. Epub 2008 Sep 8.
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 microg/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 microg/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.
抗生素的滥用已将我们这个时代推向了危险边缘，因为抗生素耐药病原体的进化速度似乎比抗生素的发明速度更快。因此，急需治疗细菌感染的新药物。阳离子宿主防御肽处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药物。在此，从毒疣大疣蛛的毒液中克隆并鉴定了一种新型阳离子宿主防御肽——疣蛛素。金黄色葡萄球菌的最低抑菌浓度为25微克/毫升，包括耐药病原体。基于疣蛛素的分子模板，通过氨基酸替换设计了疣蛛素-M1。金黄色葡萄球菌的最低抑菌浓度为5微克/毫升，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等耐药病原体。此外，疣蛛素-M1也能抑制革兰氏阴性菌。疣蛛素和疣蛛素-M1的作用方式均为通过破坏细菌细胞膜实现快速杀菌，在肽递送后，存活细菌数量立即减少约4至5个数量级。这些结果表明，疣蛛素可被视为一种潜在的抗感染药物，尤其是用于治疗耐药病原体。
