STRUCTURE/PERMEABILITY OF LIPOPOLYSACCHARIDE MEMBRANES

该项目的总体目标是确定结构， 由脂多糖（内毒素）组成的膜的渗透性 分离自各种革兰氏阴性菌。 细胞外单层 这些细菌的外膜含有一种独特的脂质， 脂多糖（LPS），其由特异性多糖组成 连接到脂质A，其含有4至7个饱和脂肪酸链。 LPS对于细菌的生长和存活是必需的， 也导致了人类的各种病理反应。 此外，LPS形成紧密的渗透性屏障，其被认为是 这些细菌对各种抗生素的耐药性至关重要。 突变细菌含有修饰的LPS，其具有不同数量的 极性成分。 已经发现， 突变细菌对疏水性 抗生素 本提案的具体目标是确定和 将组成的双层的结构和渗透性能关联起来， 突变细菌的LPS， 豁免权。 这项研究涉及X射线的综合使用 衍射，差示扫描量热法， LPS和LPS：细菌磷脂双层的渗透性测量 在存在和不存在二价阳离子的情况下。 了实验 旨在系统地测试关于角色的几个假设， LPS多糖链和平面内分子间 细菌对抗生素的敏感性的相互作用。 等 基本信息应该有助于理解物理 细菌外膜屏障功能的基础， 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.