Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2

• Main Authors: Lau, Qiu Ying, Li, Jianguo, Sani, Marc-Antoine, Sinha, Sheetal, Li, Yan, Ng, Fui Mee, Kang, CongBao, Bhattacharjya, Surajit, Separovic, Frances, Verma, Chandra, Chia, Brian Cheng San
• Other Authors: Interdisciplinary Graduate School (IGS)
• Format: Article
• Language: English
• Published: 2019
• Subjects: Antimicrobial Peptide; Membrane Disruptor; DRNTU::Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/90094; http://hdl.handle.net/10220/48405
• Institution: Nanyang Technological University

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.