Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH2

作者：Lau Qiu Ying; Li Jianguo; Sani Marc Antoine; Sinha Sheetal; Li Yan; Ng Fui Mee; Kang CongBao; Bhattacharjya Surajit; Separovic Frances; Verma Chandra; Chia Cheng San Brian^*

来源：Biochimica et Biophysica Acta-Biomembranes, 2018, 1860(8): 1517-1527.

DOI：10.1016/j.bbamem.2018.05.004

• Antimicrobial peptide
• Membrane disruptor
• Solid-state NMR
• Electron microscopy
• Dye leakage

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 mu M), 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.

• 出版日期2018-8
• 单位南阳理工学院