title: 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.
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 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.
authors.affiliation: Institut für Medizinische Mikrobiologie, Medizinische Hochschule Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hammerschmidt
authors.forename: A
authors.initials: A
authors.lastname: Müller
authors.forename: H
authors.initials: H
authors.lastname: Sillmann
authors.forename: M
authors.initials: M
authors.lastname: Mühlenhoff
authors.forename: R
authors.initials: R
authors.lastname: Borrow
authors.forename: A
authors.initials: A
authors.lastname: Fox
authors.forename: J
authors.initials: J
authors.lastname: van Putten
authors.forename: W D
authors.initials: WD
authors.lastname: Zollinger
authors.forename: R
authors.initials: R
authors.lastname: Gerardy-Schahn
authors.forename: M
authors.initials: M
authors.lastname: Frosch
mesh_terms: D000595:Amino Acid Sequence; D016667:Bacterial Capsules; D001483:Base Sequence; D015152:Blotting, Northern; D004269:DNA, Bacterial; D004196:Disease Outbreaks; D014644:Genetic Variation; D006801:Humans; D008589:Meningococcal Infections / Q000453:epidemiology / Q000382:microbiology; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism
chemical_list: D004269:DNA, Bacterial; D012799:Sialyltransferases