Kahler C M, Stephens D S
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30303, USA.
Crit Rev Microbiol. 1998;24(4):281-334. doi: 10.1080/10408419891294216.
The exclusive human pathogen Neisseria meningitidis expresses lipooligosaccharide (LOS), an endotoxin that is structurally distinct from the lipopolysaccharides (LPS) of enteric Gram-negative bacilli. Differences that appear to be biologically important occur in the composition and attachment of acyl chains to lipid A, phosphorylation patterns of lipid A, and the incorporation and phosphorylation of sugar residues in the LOS inner core. Further, unlike most enteric LPS, only two to five sugar residues are attached to the meningococcal LOS inner core, and there are no multiple repeating units of O-antigens. In contrast to Escherichia coli, where the LPS biosynthesis genes are organized as large operons, the meningococcal LOS biosynthesis genes are organized into small operons or are located individually in the chromosome. Some of these genetic loci in meningococci and gonococci display polymorphisms caused by localized chromosomal rearrangements. One mechanism of antigenic variation of meningococci LOS is the regulation of glycosyltransferase activity by slipped strand mispairing of homopolymeric tracts within the 5' end of the genes encoding these enzymes, resulting in the addition of different sugar residues to the LOS molecule. Meningococcal LOS is a critical virulence factor in N. meningitidis infections and is involved in many aspects of pathogenesis, including the colonization of the human nasopharynx, survival after bloodstream invasion, and the inflammation associated with the morbidity and mortality of meningococcemia and meningitis. Meningococcal LOS, which is a component of serogroup B meningococcal vaccines currently in clinical trials, has been proposed as a candidate for a new generation of meningococcal vaccines. The rapidly expanding knowledge of the genetic basis for biosynthesis, structure, and regulation of meningococcal LOS provides insights into unique endotoxin structures and the precise role of LOS in the pathogenesis of meningococcal disease.
人专属病原体脑膜炎奈瑟菌表达脂寡糖（LOS），这是一种内毒素，其结构与肠道革兰氏阴性杆菌的脂多糖（LPS）不同。在酰基链与脂质A的组成和连接、脂质A的磷酸化模式以及LOS内核中糖残基的掺入和磷酸化方面，似乎存在生物学上重要的差异。此外，与大多数肠道LPS不同，脑膜炎球菌LOS内核仅连接有两到五个糖残基，且不存在O抗原的多个重复单元。与大肠杆菌不同，大肠杆菌的LPS生物合成基因组织成大操纵子，而脑膜炎球菌LOS生物合成基因则组织成小操纵子或单独位于染色体中。脑膜炎球菌和淋球菌中的一些这些基因位点表现出由局部染色体重排引起的多态性。脑膜炎球菌LOS抗原变异的一种机制是通过编码这些酶的基因5'端内同聚物区段的滑链错配来调节糖基转移酶活性，从而导致向LOS分子添加不同的糖残基。脑膜炎球菌LOS是脑膜炎奈瑟菌感染中的关键毒力因子，参与发病机制的许多方面，包括人类鼻咽部的定植、血流侵袭后的存活以及与脑膜炎球菌血症和脑膜炎的发病率和死亡率相关的炎症。脑膜炎球菌LOS是目前正在临床试验中的B群脑膜炎球菌疫苗的一个组成部分，已被提议作为新一代脑膜炎球菌疫苗的候选物。对脑膜炎球菌LOS生物合成、结构和调节的遗传基础的迅速扩展的认识为独特的内毒素结构以及LOS在脑膜炎球菌病发病机制中的精确作用提供了见解。
