Interactions of polymyxin B with lipopolysaccharide-containing membranes.

Interactions of polymyxin B with lipopolysaccharide-containing membranes.
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DOI:
10.1039/d1fd00036e
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发表时间:
2021-12-24
影响因子:
3.4
通讯作者:
Bonev BB
Bonev BB
中科院分区:
化学2区
文献类型:
--
作者:
Goode A;Yeh V;Bonev BB

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细菌对抗生素的耐药性不断改变着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光谱的阳离子多肽,作为最后手段和佐剂重新投入使用。我们用荧光去猝灭的方法研究了大肠杆菌BL21中的粗化型细菌脂多糖作为脂多糖破坏细胞膜的分子促进剂的作用。多粘菌素B/脂的最小渗漏开始所需的比值从5.9×10−4增加到1.9×10−7。我们用琼脂扩散法证实了多粘菌素B对E.coliBL21的活性,并测定了其最低抑菌浓度为291μg ml−1。用31P核磁共振研究了多粘菌素对脂膜稳定性和动力学的影响以及脂多糖的作用,并用高分辨31P MAS核磁共振弛豫法监测了双层脂膜中多粘菌素B和脂多糖之间的选择性分子相互作用。我们观察到rLPS对多粘菌素B的膜裂解特性有很强的促进作用,并观察到多粘菌素B通过焦磷酸介导的特异性分子识别过程。多粘菌素B利用细菌内毒素作为对接受体穿过外膜。
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. Polymyxin B uses bacterial LPS as docking receptor to cross the outer membrane.
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期刊: FASEB JOURNAL
影响因子: 4.8
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发表时间: 1973-01-01
期刊: BIOCHEMISTRY
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DOI: 10.1021/acs.langmuir.9b03759
发表时间: 2020-08-25
期刊: LANGMUIR
影响因子: 3.9
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DOI: 10.1093/jac/dkn090
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