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毒液衍生肽 Mastoparan-1 可根除浮游和生物膜嵌入的耐甲氧西林金黄色葡萄球菌分离株。

Venom-derived peptide Mastoparan-1 eradicates planktonic and biofilm-embedded methicillin-resistant Staphylococcus aureus isolates.

机构信息

Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Microb Pathog. 2018 Jun;119:72-80. doi: 10.1016/j.micpath.2018.04.008. Epub 2018 Apr 4.

Abstract

During the past decade, cationic antimicrobial peptides (CAPs) have gained particular interest among researchers, since they often display broad-spectrum antimicrobial activity and low possibility of resistance emergence. This study aimed to investigate in vitro effectiveness of Mastoparan-1 (MP-1), a tetradecapeptide CAP from hornet venom, against methicillin-resistant Staphylococcus aureus (MRSA) isolates. MP-1 had a high propensity to form alpha-helix based on structural predictions. MP-1 was found to possess strong antimicrobial activities and weak cytotoxic effects. Multiple treatments of MRSA with MP-1 at sub-lethal dose did not induce resistance. At 4 × minimum bactericidal concentration (MBC), MP-1 eradicated bacteria within 60 min, whereas vancomycin was unable to eradicate MRSA even after 480 min of exposure, highlighting rapid bactericidal kinetics of MP-1. Treatment of bacteria with 2 × MBC of MP-1 caused a time-dependent increase in orange/red fluorescence intensity. Compared with vancomycin, MP-1 significantly reduced biofilm formation and diminished both biofilm biomass and viability of biofilm-embedded bacteria in a concentration-dependent manner. Taken together, the current data reveal not only that MP-1 is a potent bactericidal and antibiofilm agent, but also that it is less likely to invoke antimicrobial resistance, reinforcing further studies concerning the therapeutic applications of MP-1.

摘要

在过去的十年中,阳离子抗菌肽(CAPs)引起了研究人员的特别关注,因为它们通常具有广谱抗菌活性和低耐药性产生的可能性。本研究旨在研究来自大黄蜂毒液的十四肽 CAP Mastoparan-1(MP-1)对耐甲氧西林金黄色葡萄球菌(MRSA)分离株的体外有效性。基于结构预测,MP-1 具有形成α-螺旋的高倾向。研究发现 MP-1 具有很强的抗菌活性和较弱的细胞毒性。用亚致死剂量的 MP-1 多次处理 MRSA 不会诱导耐药性。在 4×最小杀菌浓度(MBC)下,MP-1 在 60 分钟内消灭了细菌,而万古霉素即使在暴露 480 分钟后也无法消灭 MRSA,突出了 MP-1 的快速杀菌动力学。用 2×MBC 的 MP-1 处理细菌会导致橙色/红色荧光强度随时间的增加。与万古霉素相比,MP-1 以浓度依赖的方式显著减少了生物膜的形成,并减少了生物膜嵌入细菌的生物膜生物量和活力。总之,这些数据不仅表明 MP-1 是一种有效的杀菌和抗生物膜剂,而且不太可能引发抗菌耐药性,进一步加强了关于 MP-1 治疗应用的研究。

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