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|Title:||Molecular genetic analysis of capsular polysaccharide biosynthesis genes in Neisseria meningitidis group B.|
|Presented at:||University of Leicester|
|Abstract:||Meningococcal meningitis is one of the most serious infectious diseases, with high mortality rates in spite of antibiotic therapy. Although polysaccharide-based vaccines have been developed to Neisseria meningitidis (meningococcus) groups A, C, W135 and Y, there is, as yet, no effective vaccine against serogroup B meningococcus. The capsular polysaccharides of Neisseria meningitidis group B and Escherichia coli K1 are identical and the pathways of biosynthesis similar. Molecular genetic analysis, performed prior to any published data, has revealed the organisation of the genes involved in biosynthesis and polymerisation of alpha2,8- linked N-acetylneuraminic acid in N. meningitidis group B. The biosynthetic region contains four genes, three of which appear to be organised in an operon. Northern blot analysis revealed a 2.85kb transcript which correlates well with the size of the predicted transcript for the operon. The proteins encoded by the four genes are similar to the products of the neuA, neuB, neuC and neuS genes of the E. coli K1 capsular polysaccharide gene cluster. In contrast to previous studies (Echarti et al., 1983), Southern hybridisation analysis demonstrated similarity between the cloned meningococcal group B capsule genes and the cloned E. coli K1 capsular polysaccharide genes. The DNA and predicted protein similarities substantiate the theory of the common evolutionary origin of encapsulation in these two unrelated bacteria. Additional novel findings are the demonstration of a similar biosynthetic pathway of capsule production in all sialic acid-encapsulated meningococcal serogroups, and a common mechanism of transport. Studies on the molecular organisation and control of capsule gene expression are fundamental to the successful development of a meningococcus group B vaccine, or to the progression of alternative therapeutic approaches for treatment of infections by sialic acid-encapsulated organisms.|
|Rights:||Copyright © the author. All rights reserved.|
|Appears in Collections:||Theses, Dept. of Biology|
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