1887

Abstract

strains express a diverse range of lipopolysaccharide (LPS) structures that have been classified into 12 immunotypes. A feature of meningococcal LPS is the reversible, high-frequency switching of expression (phase variation) of terminal LPS structures. A number of studies are strongly suggestive of a key role for these terminal structures, and their phase-variable expression, in pathogenesis. In a previous study, a locus of three LPS biosynthetic genes, , involved in the biosynthesis of one of these terminal structures, lacto--neotetraose, was described. The molecular mechanism of phase-variable expression of this structure is by high-frequency mutation in a homopolymeric tract of G residues in the gene. To investigate the genetic basis of the structural differences between the immunotypes, and the potential for strains to express alternative immunotypes, this locus was examined in all of the immunotype strains. Initially, the locus of strain 126E, an L1 immunotype strain, was cloned and sequenced, revealing two active genes, and . The remnants of the and genes and an inactive gene were also present, indicating that the locus may have once contained five active genes, similar to a locus previously reported in strain F62. Probes based on each of the genes (), and the recently reported gene, were used to determine the presence or absence of genes within individual strains, allowing the prediction of the phase variation repertoire of these strains. Sequencing to determine the nature of homopolymeric tract regions within the genes was carried out to establish the potential for LPS switching. In general, the set of strains examined could be sorted into two distinct groups: one group which phase-vary the α-chain extension via or but cannot make β-chain; the second group phase-vary the β-chain extension via but do not vary α-chain (lacto--neotetraose).

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1999-11-01
2020-04-08
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