Lipooligosaccharide (LOS) is a major surface antigen and a virulence factor of Neisseria meningitidis. It can be serologically divided into 12 LOS immunotypes. Epidemiological studies in recent years have revealed that the L3,7 immunotype is the most common immunotype among serogroups B and C strains causing disease, the predominant serogroups of meningococcal disease in the North and South America and Europe. Besides their capsular polysaccharides, sialylation of LOS enhances these two serogroup organisms to resist killing by normal human serum. We have shown that the a-chain length, that extends out from heptose (I) of LOS, influenced its sialylation in N. meningitidis. The a-chain required a terminal Gal and a trisaccharide or higher oligosaccharide to serve as acceptor for the LOS sialyltransferase in sialylation. The disaccharide a-chain, lactose (Galb1-4Glc), in an immunotype L8 LOS could not be sialylated. Genetic and chemical data indicate that the non-sialylation of L8 LOS is probably due to steric hindrance imposed by the neighboring second heptose (II) in the inner core with a phosphorylethanolamine attachment. For the past decade, epidemiological surveys showed that meningococcal Group C disease was mainly caused by serotype 2a and subtype P1.2,5. However, in 2000-2001, an unusual Group C:2a:P1.1,7 was found in 32 out of 52 (61%) Group C disease isolates in Quebec Province, Canada. In a collaboratory study, we have biochemically and genetically characterized eight strains Group of C:2a:P1.1,7 from Canada including six representative Quebec strains. The LOS in the most strains was quite heterogeneous with 5 or more components seen on SDS-PAGE gel. All six Quebec strains had L2 as the major LOS immunotype. Their LOS biosynthesis genes had the same gene organization, lgtABH. For the other two Toronto strains had L2 or L5 as the major immunotype with the gene organization of lgtABH. Sequence analysis of the three genes in two of L2 strains and the L5 strain revealed that only one base pair nonsynonymous mutation in lgtH of the L5 strain. The results indicated that the unusual Group C:2a:P1.1,7 disease strains in Quebec were from the same clone and the other L5 strain was closely related.

Agency
National Institute of Health (NIH)
Institute
Center for Biologics Evaluation and Research - Bactrial Products (CBERBP)
Type
Intramural Research (Z01)
Project #
1Z01BJ002010-09
Application #
6677900
Study Section
Large Bowel and Pancreatic Cancer Review Committee (LBP)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2002
Total Cost
Indirect Cost