Bacterial resistance to antibiotics constantly remodels the battlefront between infections and antibiotic therapy. Polymyxin B, a cationic peptide with an anti-Gram-negative spectrum of activity is re-entering use as a last resort measure and as an adjuvant. We use fluorescence dequenching to investigate the role of the rough chemotype bacterial lipopolysaccharide from E. coli BL21 as a molecular facilitator of membrane disruption by LPS. The minimal polymyxin B/lipid ratio required for leakage onset increased from 5.9 × 10⁻⁴ to 1.9 × 10⁻⁷ in the presence of rLPS. We confirm polymyxin B activity against E. coli BL21 by the agar diffusion method and determined a MIC of 291 μg ml⁻¹. Changes in lipid membrane stability and dynamics in response to polymyxin and the role of LPS are investigated by ³¹P NMR and high resolution ³¹P MAS NMR relaxation is used to monitor selective molecular interactions between polymyxin B and rLPS within bilayer lipid membranes. We observe a strong facilitating effect from rLPS on the membrane lytic properties of polymyxin B and a specific, pyrophosphate-mediated process of molecular recognition of LPS by polymyxin B.

中文翻译：

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多粘菌素 B 与含脂多糖膜的相互作用

细菌对抗生素的耐药性不断重塑感染和抗生素治疗之间的战线。多粘菌素 B 是一种具有抗革兰氏阴性活性谱的阳离子肽，作为最后的手段和佐剂重新进入使用。我们使用荧光去猝灭来研究来自大肠杆菌BL21 的粗糙化学型细菌脂多糖作为 LPS 膜破坏的分子促进剂的作用。在rLPS 存在下，泄漏开始所需的最小多粘菌素B/脂质比从5.9 × 10 ^-4增加到1.9 × 10 ^{-7 。}我们通过琼脂扩散法确认多粘菌素 B 对大肠杆菌BL21 的活性，并确定 MIC 为 291 μg ml ^-1. ^通过31 P NMR研究了响应多粘菌素的脂质膜稳定性和动力学的变化以及 LPS 的作用，高分辨率³¹ P MAS NMR 弛豫用于监测双层脂质膜内多粘菌素 B 和 rLPS 之间的选择性分子相互作用。我们观察到 rLPS 对多粘菌素 B 的膜裂解特性的强烈促进作用以及多粘菌素 B 对 LPS 的特异性、焦磷酸介导的分子识别过程。