STRUCTURE/PERMEABILITY OF LIPOPOLYSACCHARIDE MEMBRANES

该项目的总体目标是确定结构和 脂多糖(内毒素)组成的膜的通透性 从各种革兰氏阴性细菌中分离出来的。的外单分子层 这些细菌的外膜含有一种独特的脂类，称为 脂多糖(LPS)，由特定的多糖类组成 与脂类A相连，它含有4到7条饱和脂肪链。 内毒素对细菌的生长和生存是必不可少的，而且 也对人类的各种病理反应负责。 此外，内毒素形成了一种紧密的通透性屏障，被认为是 对这些细菌对各种抗生素的抗药性至关重要。 突变细菌含有不同数量的修饰LPS 糖类和极地成分。已经发现，特定的 突变细菌对疏水的敏感性完全不同。 抗生素。这项提案的具体目标是确定和 将组成的双层的结构和渗透性相关联 来自表现出一系列抗生素的突变细菌的LPS 易感性。这项研究涉及联合使用X射线 衍射法、差示扫描量热法和抗菌剂 细菌磷脂双层膜对内毒素和内毒素通透性的测定 在存在和不存在二价阳离子的情况下。这些实验是 旨在系统地测试关于角色的几个假设 脂多糖多糖链和平面分子间的相互作用 细菌对抗生素敏感性的相互作用。是这样的 基本信息应该有助于理解物理 细菌外膜屏障功能的基础和 抗生素进入细胞的机制。

The overall goals of this project are to determine the structure and permeability of membranes composed of lipopolysaccharides (endotoxins) isolated from various Gram-negative bacteria. The outer monolayer of the outer membrane of these bacteria contains a unique lipid called lipopolysaccaride (LPS), which consists of specific polysaccarides linked to lipid A, which contains 4 to 7 saturated fatty acid chains. LPS is essential for the growth and survival of the bacterium and is also responsible for a variety of pathological reactions in humans. Moreover, LPS forms a tight permeability barrier which is thought to be critical for the resistance of these bacteria to various antibiotics. Mutant bacteria contain modified LPSs with different numbers of saccharides and polar constitutents. It has been found that specific mutant bacteria have quite different susceptibilities to hydrophobic antibiotics. The specific aims of this proposal are to determine and correlate the structure and permeability properties of bilayers composed of LPSs from mutant bacteria which exhibit a range of antibiotic susceptibilities. The research involves the combined use of X-ray diffraction, differential scanning calorimetry, and antibiotitic permeability measurements of LPS and LPS:bacterial phospholipid bilayers in the presence and absence of divalent cations. The experiments are designed to test systematically several hypotheses concerning the role of the LPS polysaccharide chains and in-plane intermolecular interactions to the susceptibility of bacteria to antibiotics. Such fundamental information should be useful in understanding the physical basis of the barrier function of the bacterial outer membrane and the mechanisms involved in antibiotic entry into the cell.