Trent M Stephen, Stead Christopher M, Tran An X, Hankins Jessica V
Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, USA.
J Endotoxin Res. 2006;12(4):205-23. doi: 10.1179/096805106X118825.
Lipopolysaccharide or LPS is localized to the outer leaflet of the outer membrane and serves as the major surface component of the bacterial cell envelope. This remarkable glycolipid is essential for virtually all Gram-negative organisms and represents one of the conserved microbial structures responsible for activation of the innate immune system. For these reasons, the structure, function, and biosynthesis of LPS has been an area of intense research. The LPS of a number of bacteria is composed of three distinct regions--lipid A, a short core oligosaccharide, and the O-antigen polysaccharide. The lipid A domain, also known as endotoxin, anchors the molecule in the outer membrane and is the bioactive component recognized by TLR4 during human infection. Overall, the biochemical synthesis of lipid A is a highly conserved process; however, investigation of the lipid A structures of various organisms shows an impressive amount of diversity. These differences can be attributed to the action of latent enzymes that modify the canonical lipid A molecule. Variation of the lipid A domain of LPS serves as one strategy utilized by Gram-negative bacteria to promote survival by providing resistance to components of the innate immune system and helping to evade recognition by TLR4. This review summarizes the biochemical machinery required for the production of diverse lipid A structures of human pathogens and how structural modification of endotoxin impacts pathogenesis.
脂多糖（LPS）定位于外膜的外小叶，是细菌细胞壁包膜的主要表面成分。这种非凡的糖脂对几乎所有革兰氏阴性菌都是必不可少的，是负责激活先天免疫系统的保守微生物结构之一。由于这些原因，LPS的结构、功能和生物合成一直是深入研究的领域。许多细菌的LPS由三个不同区域组成——脂质A、一个短的核心寡糖和O抗原多糖。脂质A结构域，也称为内毒素，将分子锚定在外膜中，是人类感染期间TLR4识别的生物活性成分。总体而言，脂质A的生化合成是一个高度保守的过程；然而，对各种生物体脂质A结构的研究表明存在大量差异。这些差异可归因于修饰典型脂质A分子的潜在酶的作用。LPS脂质A结构域的变异是革兰氏阴性菌利用的一种策略，通过对先天免疫系统成分产生抗性并帮助逃避TLR4识别来促进生存。本综述总结了产生人类病原体多种脂质A结构所需的生化机制，以及内毒素的结构修饰如何影响发病机制。
