Determination of the mechanism of bacterial membrane disruption by cationic antimicrobial polymers

Rising antimicrobial resistance poses one of the largest threats to global health, predicted to lead to over 10 million deaths per annum in the UK and US alone by 2050. To combat this issue, we have taken inspiration from natural antimicrobial peptides and developed a library of synthetic, cationic antimicrobial polymers which are effective in inhibiting the growth of clinically relevant MRSA by disrupting the membranes which encapsulate the bacterial cell. Here, we propose to assemble planar floating lipid bilayers containing anionic lipids on functionalised gold surfaces to mimic bacterial membranes. By using neutron reflectometry and exploiting isotopic contrast variation, we aim to determine the mechanism of membrane disruption by cationic antimicrobial peptides whilst obtaining insight into how the properties of these materials infljuence their antimicrobial efficacy.

不断升级的抗菌药物耐药性已成为全球健康面临的重大威胁之一，据预测，到2050年，仅英国和美国两国每年就将因此导致超过1000万人死亡。为应对这一公共卫生危机，研究团队从天然抗菌肽（antimicrobial peptides）中汲取灵感，开发了一套合成阳离子抗菌聚合物库。这类聚合物可通过破坏包裹细菌细胞的细胞膜，有效抑制临床相关耐甲氧西林金黄色葡萄球菌（MRSA）的增殖。本研究拟在功能化金表面组装负载阴离子脂质的平面浮动脂质双分子层，以模拟细菌细胞膜结构。本研究将采用中子反射术（neutron reflectometry）并利用同位素衬度变化技术，旨在阐明阳离子抗菌肽破坏细胞膜的作用机制，同时深入探究这类材料的自身属性如何影响其抗菌效能。