Genetics of Neisseria meningitidis lipooligosaccharide

脑膜炎奈瑟菌脂寡糖的遗传学

• 批准号: 6543589
• 负责人: Peixuan Zhu
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6543589
• 关键词: Neisseria meningitidis; bacterial antigens; bacterial genetics; bacterial meningitis; chemical structure function; communicable disease transmission; genetic strain; glycolipids; glycosyltransferase; nucleic acid hybridization; nucleic acid sequence; polymerase chain reaction; virulence; virus classification

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.

摘要：脑膜炎球菌脑膜炎仍然是全球重大的健康问题。脑膜炎链球菌的脂肪糖（LOS）是外膜和主要毒力因子的主要组成部分。已经表明，LOS的寡糖链模拟了红细胞和其他组织的表面上的人糖磷脂。基于寡糖链的结构中的抗原变异，将脑膜炎链球菌的洛杉矶分为12种Immonotypes（L1-L12）。首次在淋病奈瑟氏菌中鉴定出七个编码糖基转移酶的七个LGT基因，这些染色体基因座编码糖基转移酶，负责寡糖链的生物合成。 LGT同源物已被测序的三种脑膜炎菌菌株，126E（L1），MC58（L3）和Z2491（L9）。 在不同的生长条件下，在两种脑膜炎菌株M978和A1中观察到L8-LOS免疫型表达的变化和稳定性。已经确定了两个菌株的LGT基因座的核苷酸序列。通过将两个新型遗传组织与数据库中的脑膜炎和淋病链球菌的LGT序列进行了比较，已经在这两个菌株中发现了两个新的遗传组织。菌株M978包含5个与LGTC，A，B，E和由部分LGTA和LGTB组成的Mosaic ORF（LGTZ）的ORF。菌株A1仅包含两个基因，即LGTA和LGTH。数据表明，LGT遗传成分和排列是确定脑膜炎链球菌表达的变异和稳定性的重要因素之一。 现在也确定了其余9个免疫型的三个LGT基因座的DNA序列。为了进行比较，还通过PCR和DNA杂交检测了非对病毒奈瑟氏菌中的LGT基因。根据三个染色体基因座的LGT基因的组成和组织提出了LOS遗传分型方案。评估了LGT基因在致病性和非致病性奈瑟氏菌种类中的系统发育关系和进化史。目前正在使用与加拿大魁北克的2001年脑膜炎球菌疾病爆发相关的血清群C菌株进行流行病学研究的应用。