Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH2, with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 μM), the main causative pathogen of human skin infections with an unknown mechanism of action. Herein, we describe a series of experiments conducted to gain further insights into its mechanism of action involving electron microscopy, artificial membrane dye leakage, solution- and solid-state NMR spectroscopy followed by molecular dynamics simulations. Experimental results point towards a SMART (Soft Membranes Adapt and Respond, also Transiently) mechanism of action, suggesting that the peptide can be developed as a topical antibacterial agent for treating drug-resistant Staphylococcus aureus infections.

中文翻译：

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阐明线性抗菌四肽BRBR-NH2的作用机理。

线性抗菌肽，具有快速的杀菌作用，非常适合作为局部抗菌药物开发。我们最近设计了一种合成的线性4残基肽BRBR-NH2，具有对金黄色葡萄球菌（MIC 6.25μM）的强力杀菌活性，金黄色葡萄球菌是人类皮肤感染的主要致病菌，其作用机理未知。在这里，我们描述了一系列的实验，以进一步了解其作用机理，包括电子显微镜，人工膜染料泄漏，溶液和固态NMR光谱，然后进行分子动力学模拟。实验结果指向一种SMART（软膜适应和响应，也可以是暂时的）作用机制，