Genetics of Neisseria meningitidis lipooligosaccharide

总结： 脑膜炎球菌性脑膜炎仍然是世界范围内的一个重大健康问题。对N.脑膜炎是外膜的主要成分，也是主要的毒力因子。已显示LOS的寡糖链模拟红细胞和其它组织表面上的人鞘糖脂。N的LOS。根据寡糖链结构的抗原性变化，脑膜炎分为12种免疫单型（L1-L12）。七个lgt基因在三个染色体位点编码糖基转移酶，负责寡糖链的生物合成，首先在淋病奈瑟氏菌。已对三种N.脑膜炎，126 E（L1），MC 58（L3）和Z2491（L9）。 L 8-LOS免疫型的表达在两个N.脑膜炎球菌菌株M978和A1在不同生长条件下的生长。测定了这两个菌株lgt基因座的核苷酸序列。通过与N.脑膜炎和脑膜炎奈瑟氏球菌（N.数据库里的淋病病毒菌株M978含有5个与lgtC、A、B、E同源的ORF和一个由部分lgtA和lgtB组成的嵌合ORF（lgtZ）。菌株A1仅含有两个基因，lgtA和lgtH。说明lgt基因的遗传组成和排列是决定氮素表达变异和稳定性的重要因素之一。脑膜炎 其余9种免疫型的3个lgt基因座的DNA序列也已确定。为了比较，非致病性奈瑟菌的lgt基因也通过PCR和DNA杂交检测。根据三个染色体位点lgt基因的组成和结构，提出了一种LOS基因分型方案。评价了致病性和非致病性奈瑟菌lgt基因的系统发育关系和进化历史。目前正在利用与2001年加拿大魁北克脑膜炎球菌病爆发有关的血清群C菌株，将LOS基因分型系统应用于流行病学调查。

Summary: Meningococcal meningitis remains a significant health problem worldwide. The lipooligosaccharide (LOS) of N. meningitidis is a major component of the outer membrane and a major virulence factor. It has been shown that the oligosaccharide chain of LOS mimics human glycosphingolipids on the surfaces of erythrocytes and other tissues. The LOS of N. meningitidis was divided into 12 immonotypes (L1-L12) based on antigenic variations in the structure of the oligosaccharide chains. Seven lgt genes at three chromosomal loci encoding glycosyltransferase, responsible for the biosynthesis of oligosaccharide chains, were first identified in Neisseria gonorrhoeae. The lgt homologues have been sequenced for three strains of N. meningitidis, 126E (L1), MC58 (L3) and Z2491 (L9). Variation and stability in expression of the L8-LOS immunotype was observed in two N. meningitidis strains, M978 and A1, under different growth conditions. The nucleotide sequences of the lgt locus for theses two strains have been determined. Two novel genetic organizations have been identified in these two strains by comparing them to the lgt sequences of N. meningitidis and N. gonorrhoeae in the databases. Strain M978 contains 5 ORFs that had homology to lgtC, A, B, E and a mosaic ORF (lgtZ) consisting of the partial lgtA and lgtB. Strain A1 contains only two genes, lgtA and lgtH. The data demonstrated that the lgt genetic components and arrangement is one of the important factors to determine variation and stability of expression of N. meningitidis LOS. DNA sequences of three lgt loci for the remaining 9 immunotypes have now been determined as well. For comparison, the lgt genes in nonpathogenic Neisseria species were also detected by PCR and DNA hybridization. A LOS genetic typing scheme was proposed based on the composition and organization of the lgt genes at three chromosomal loci. The phylogenetic relationships and evolutionary history of the lgt genes in pathogenic and nonpathogenic Neisseria species were evaluated. Application of the LOS genetic typing system for the epidemiological investigation is currently being worked on using Serogroup C strains associated with the 2001 meningococcal disease outbreak in Quebec, Canada.