Genetics of Neisseria meningitidis lipooligosaccharide

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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.