Abstract
ABSTRACTStreptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions.
Highlights
Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings
The polysaccharide capsule is known to influence multiple aspects of pneumococcal biology. Serotypes vary in their nasopharyngeal carriage rates [21], and their propensity to cause IPD was usually expressed as the “invasive potential” in order to account for the various exposures to different serotypes (22Ϫ24)
We sequenced the genomes of 439 Streptococcus pneumoniae clinical isolates collected from the Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, between 2002 and 2010
Summary
We sequenced the genomes of 439 Streptococcus pneumoniae clinical isolates collected from the Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi (southeastern Africa), between 2002 and 2010. For the analysis of serotype-specific evolution of lineages identified as described below, SNPs were called against reference genomes (Table S2). Analysis of the population using BAPS [33, 34] identified 14 primary sequence clusters (SCs) (Fig. 1). Of these 14 SCs, SC1 to SC13 were monophyletic clades. Most SCs contained isolates with a single serotype and multiple closely related sequence types (STs) as determined by multilocus sequence typing (MLST) (Fig. 1; see Table S1 in the supplemental material). The subclade with serotype 35B in SC9 contained additional serotypes with the same ST that were extremely closely related at the whole-genome level (Fig. 1), which suggests that this subclade was a single lineage of serotype 35B that recently acquired other capsule types.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
