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

Sven Hammerschmidt, Astrid Müller, Hanna Sillmann, Martina Mühlenhoff, Raymond Borrow, Andrew Fox, Jos Van Putten, Wendell D. Zollinger, Rita Gerardy-Schahn, Matthias Frosch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

197 Citations (Scopus)

Abstract

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 α-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 sleD, 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.

Original languageEnglish
Pages (from-to)1211-1220
Number of pages10
JournalMolecular Microbiology
Volume20
Issue number6
DOIs
Publication statusPublished - 1996
Externally publishedYes

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