Capsule phase variation in Neisseria meningitidis serogroup B by slipped-strand mispairing in the polysialyltransferase gene (siaD): correlation with bacterial invasion and the outbreak of meningococcal disease

Mol Microbiol. 1996 Jun;20(6):1211-20. doi: 10.1111/j.1365-2958.1996.tb02641.x.


A mechanism of capsular polysaccharide phase variation in Neisseria meningitidis is described. Meningococcal cells of an encapsulated serogroup B strain were used in invasion assays. Only unencapsulated variants were found to enter epithelial cells. Analysis of one group of capsule-deficient variants indicated that the capsular polysaccharide was re-expressed at a frequency of 10(-3). Measurement of enzymatic activities involved in the biosynthesis of the alpha-2,8 polysialic acid capsule showed that polysialyltransferase (PST) activity was absent in these capsule-negative variants. Nucleotide sequence analysis of siaD revealed an insertion or a deletion of one cytidine residue within a run of (dC)7 residues at position 89, resulting in a frameshift and premature termination of translation. We analysed unencapsulated isolates from carriers and encapsulated case isolates collected during an outbreak of meningococcal disease. Further paired blood-culture isolates and unencapsulated nasopharyngeal isolates from patients with meningococcal meningitis were examined. In all unencapsulated strains analysed we found an insertion or deletion within the oligo-(dC) stretch within siaD, resulting in a frameshift and loss of capsule formation. All encapsulated isolates, however, had seven dC residues at this position, indicating a correlation between capsule phase variation and bacterial invasion and the outbreak of meningococcal disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Capsules
  • Base Sequence
  • Blotting, Northern
  • DNA, Bacterial
  • Disease Outbreaks
  • Genetic Variation
  • Humans
  • Meningococcal Infections / epidemiology
  • Meningococcal Infections / microbiology
  • Molecular Sequence Data
  • Neisseria meningitidis / genetics*
  • Neisseria meningitidis / isolation & purification
  • Neisseria meningitidis / pathogenicity*
  • Sequence Analysis, DNA
  • Sialyltransferases / genetics*
  • Sialyltransferases / metabolism


  • DNA, Bacterial
  • Sialyltransferases