Qiu Ying Lau, Jianguo Li, Marc-Antoine Sani, Sheetal Sinha, Yan Li, Fui Mee Ng, CongBao Kang, Surajit Bhattacharjya, Frances Separovic, Chandra Verma, Cheng San Brian Chia, Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH2, Biochimica et Biophysica Acta (BBA) - Biomembranes, Available online 11 May 2018, ISSN 0005-2736, https://doi.org/10.1016/j.bbamem.2018.05.004.
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 uM), 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.
Agency for Science, Technology and Research (A*STAR) Biomedical Research Council, Australian Research Council (ARC) grant LE160100120, Singapore Ministry of Education (MOE) grant ARC 18/13.