Abstract
The main virulence factor of Streptococcus pneumoniae is the capsule. The polysaccharides comprising this capsule are encoded by approximately 15 genes and differences in these genes result in different serotypes. The aim of this study was to investigate the sequence diversity of the capsular genes of serotypes 6A, 6B, 6C, 19A and 19F and to explore a possible effect of vaccination on variation and distribution of these serotypes in the Netherlands. The complete capsular gene locus was sequenced for 25 serogroup 6 and for 20 serogroup 19 isolates. If one or more genes varied in 10 or more base pairs from the reference sequence, it was designated as a capsular subtype. Allele-specific PCRs and specific gene sequencing of highly variable capsular genes were performed on 184 serogroup 6 and 195 serogroup 19 isolates to identify capsular subtypes. This revealed the presence of 6, 3 and a single capsular subtype within serotypes 6A, 6B and 6C, respectively. The serotype 19A and 19F isolates comprised 3 and 4 capsular subtypes, respectively. For serogroup 6, the genetic background, as determined by multi locus sequence typing (MLST) and multiple- locus variable number of tandem repeat analysis (MLVA), seemed to be closely related to the capsular subtypes, but this was less pronounced for serogroup 19 isolates. The data also suggest shifts in the occurrence of capsular subtypes within serotype 6A and 19A after introduction of the 7-valent pneumococcal vaccine. The shifts within these non-vaccine serotypes might indicate that these capsular subtypes are filling the niche of the vaccine serotypes. In conclusion, there is considerable DNA sequence variation of the capsular genes within pneumococcal serogroup 6 and 19. Such changes may result in altered polysaccharides or in strains that produce more capsular polysaccharides. Consequently, these altered capsules may be less sensitive for vaccine induced immunity.
Highlights
Streptococcus pneumoniae, the pneumococcus, is responsible for infections such as meningitis, pneumonia and otitis media
We observed considerable variations among the capsular genes within serotypes which enabled us to assign capsular subtypes based on the sequence of the entire capsular locus
The largest number of capsular subtypes was found among serotype 6A, but in serotype 6B the highest degree of sequence variation between capsular subtypes was found
Summary
Streptococcus pneumoniae, the pneumococcus, is responsible for infections such as meningitis, pneumonia and otitis media. The main virulence factor of the pneumococcus is its polysaccharide capsule. It protects the bacteria against phagocytosis and plays an important role in colonization of the upper airways [1]. The genes encoding the polysaccharides are located within the capsular gene locus and have a similar arrangement in most serotypes. At the 59 end, next to dexB, the genes for regulation and translocation are located. These genes, designated wzg, wzh, wzd and wze, are relatively conserved in all serotypes [7]. The genes involved in the synthesis of the polysaccharide and encoding glycosyltransferases, flippases and polymerases are located downstream of the regulatory genes. All different polysaccharides are synthesized by this pathway except serotype 3 and 37 polysaccharides which are synthesized by the synthase-dependent pathway, using the synthase-encoding gene tts which is located elsewhere on the chromosome [6,10]
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