The Effect of Lipopolysaccharide Core Oligosaccharide Size on the Electrostatic Binding of Antimicrobial Proteins to Models of the Gram Negative Bacterial Outer Membrane.
The Effect of Lipopolysaccharide Core Oligosaccharide Size on the Electrostatic Binding of Antimicrobial Proteins to Models of the Gram Negative Bacterial Outer Membrane.
复制标题
DOI：
10.1021/acs.langmuir.6b00240
复制
发表时间：
2016-04-12
期刊：
影响因子：
--
通讯作者：
Lakey JH
中科院分区：
文献类型：
--
作者：
Clifton LA;Ciesielski F;Skoda MW;Paracini N;Holt SA;Lakey JH
了解细菌膜和外源蛋白之间的静电相互作用对于设计针对革兰氏阴性菌的有效抗菌剂至关重要。在这里，我们研究，使用中子反射法在多种同位素对比条件下，在保护富含磷酸盐的内核区域与抗微生物蛋白的静电相互作用的脂多糖（LPS）的外核区域的不带电的糖基的作用。在硅上制备不对称革兰氏阴性外膜模型，其中内瓣叶（最靠近硅）中使用磷酸胆碱（PC），而粗糙LPS用于形成外瓣叶（面向本体溶液）。我们展示了如何盐浓度可以用来可逆地改变蛋白质抗生素大肠杆菌素N（ColN）的结合亲和力的阴离子LPS确认的相互作用是静电的性质。通过研究ColN与两种具有不同大小的核心寡糖区域的粗糙LPS类型的相互作用，我们证明了不带电的糖在阻断阳离子抗生素和脆弱的阴离子磷酸盐基团之间的短程静电相互作用中的作用。
Understanding the electrostatic interactions between bacterial membranes and exogenous proteins is crucial to designing effective antimicrobial agents against Gram-negative bacteria. Here we study, using neutron reflecometry under multiple isotopic contrast conditions, the role of the uncharged sugar groups in the outer core region of lipopolysaccharide (LPS) in protecting the phosphate-rich inner core region from electrostatic interactions with antimicrobial proteins. Models of the asymmetric Gram negative outer membrane on silicon were prepared with phopshatidylcholine (PC) in the inner leaflet (closest to the silicon), whereas rough LPS was used to form the outer leaflet (facing the bulk solution). We show how salt concentration can be used to reversibly alter the binding affinity of a protein antibiotic colicin N (ColN) to the anionic LPS confirming that the interaction is electrostatic in nature. By examining the interaction of ColN with two rough LPS types with different-sized core oligosaccharide regions we demonstrate the role of uncharged sugars in blocking short-range electrostatic interactions between the cationic antibiotics and the vulnerable anionic phosphate groups.