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. 2014 Feb 1;209(3):377-88.
doi: 10.1093/infdis/jit481. Epub 2013 Sep 5.

Intraclonal variations among Streptococcus pneumoniae isolates influence the likelihood of invasive disease in children

Sarah Browall  1 , Martin Norman, Jeanette Tångrot, Ilias Galanis, Karin Sjöström, Jessica Dagerhamn, Christel Hellberg, Anuj Pathak, Tiziana Spadafina, Andreas Sandgren, Patrick Bättig, Oscar Franzén, Björn Andersson, Åke Örtqvist, Staffan Normark, Birgitta Henriques-Normark
Affiliations

Intraclonal variations among Streptococcus pneumoniae isolates influence the likelihood of invasive disease in children

Sarah Browall et al. J Infect Dis. .

Abstract

Background: Pneumococcal serotypes are represented by a varying number of clonal lineages with different genetic contents, potentially affecting invasiveness. However, genetic variation within the same genetic lineage may be larger than anticipated.

Methods: A total of 715 invasive and carriage isolates from children in the same region and during the same period were compared using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Bacterial genome sequencing, functional assays, and in vivo virulence mice studies were performed.

Results: Clonal types of the same serotype but also intraclonal variants within clonal complexes (CCs) showed differences in invasive-disease potential. CC138, a common CC, was divided into several PFGE patterns, partly explained by number, location, and type of temperate bacteriophages. Whole-genome sequencing of 4 CC138 isolates representing PFGE clones with different invasive-disease potentials revealed intraclonal sequence variations of the virulence-associated proteins pneumococcal surface protein A (PspA) and pneumococcal choline-binding protein C (PspC). A carrier isolate lacking PcpA exhibited decreased virulence in mice, and there was a differential binding of human factor H, depending on invasiveness.

Conclusions: Pneumococcal clonal types but also intraclonal variants exhibited different invasive-disease potentials in children. Intraclonal variants, reflecting different prophage contents, showed differences in major surface antigens. This suggests ongoing immune selection, such as that due to PspC-mediated complement resistance through varied human factor H binding, that may affect invasiveness in children.

Keywords: PcpA; PspA; PspC; Streptococcus pneumoniae; bacteriophages; factor H binding; intraclonal variation; invasive disease potential; pneumococcal infections; surface proteins.

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Figures

Figure 1.
Figure 1.
Genomic differences between (A) invasive BHN191 from SWEB-3 and carriage BHN418 from SWEB-2 and (B) between invasive BHN237 and carriage BHN427, both from SWE6B-1.
Figure 2.
Figure 2.
Factor H binding to the 4 strains of 6B and clonal complex 138, using Far Western blotting.
Figure 3.
Figure 3.
Survival of mice (A) and the number of colony-forming units (CFU) in the bloodstream at 24 hours (B) after intranasal challenge with the 4 strains of serotype 6B and clonal complex 138 representing clonal types with pulsed-field gel electrophoresis patterns indicating different invasive-disease potentials. *P < .05.
See this image and copyright information in PMC

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