Intraclonal Variations Among Streptococcus pneumoniae Isolates Influence the Likelihood of Invasive Disease in Children

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.

Polysaccharide-Specific Memory B Cells Predict Protection against Experimental Human Pneumococcal Carriage

“…In cohort A, each volunteer was inoculated with 35,375 6 2,651 cfu per naris of Streptococcus pneumoniae serotype 6B (strain BHN418) ( Table 1) (14). In cohort B, each volunteer was inoculated with 61,944 6 4,603 cfu/naris of S. pneumoniae serotype 6B (Table 1).…”

Pneumococcal meningitis is promoted by single cocci expressing pilus adhesin RrgA

“…The most common causes of bacterial meningitis, Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Neisseria meningitidis (1,2), are small in size. However, during nasopharyngeal colonization, S. pneumoniae grows in chains of ovoid-shaped cocci that vary in length depending on the completeness of the cell wall cleavage between daughter cells after cell division.…”

“…Chain formation is believed to allow better adherence to the respiratory epithelium than is seen with small, individual cocci (3). Pneumococcal serotype 6B has been shown to be one of the most frequently found serotypes causing meningitis (1,2). Meningitis is usually caused by bacteria crossing from the bloodstream into the brain through the blood-brain barrier (BBB) (4).…”

Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types

“…Furthermore, pneumococci are genetically diverse due to an efficient DNA transformation system and molecular typing regimes can distinguish a number of genetically related clonal lineages that might express different capsular serotypes [2,3,16]. It is not clear to what extent invasiveness, disease manifestation and severity correlate to other properties reflected by the clonal type, such as virulence genes [22].…”