Abstract
Streptococcus pneumoniae isolates typically express one of over 90 immunologically distinguishable polysaccharide capsules (serotypes), which can be classified into “serogroups” based on cross-reactivity with certain antibodies. Pneumococci can alter their serotype through recombinations affecting the capsule polysaccharide synthesis (cps) locus. Twenty such “serotype switching” events were fully characterised using a collection of 616 whole genome sequences from systematic surveys of pneumococcal carriage. Eleven of these were within-serogroup switches, representing a highly significant (p < 0.0001) enrichment based on the observed serotype distribution. Whereas the recombinations resulting in between-serogroup switches all spanned the entire cps locus, some of those that caused within-serogroup switches did not. However, higher rates of within-serogroup switching could not be fully explained by either more frequent, shorter recombinations, nor by genetic linkage to genes involved in β–lactam resistance. This suggested the observed pattern was a consequence of selection for preserving serogroup. Phenotyping of strains constructed to express different serotypes in common genetic backgrounds was used to test whether genotypes were physiologically adapted to particular serogroups. These data were consistent with epistatic interactions between the cps locus and the rest of the genome that were specific to serotype, but not serogroup, meaning they were unlikely to account for the observed distribution of capsule types. Exclusion of these genetic and physiological hypotheses suggested future work should focus on alternative mechanisms, such as host immunity spanning multiple serotypes within the same serogroup, which might explain the observed pattern.
Highlights
Streptococcus pneumoniae is a human nasopharyngeal commensal bacterium and important respiratory pathogen
Current anti-pneumococcal vaccines target the bacterium’s polysaccharide capsule, of which at least 95 different variants (‘serotypes’) are known, which are classified into ‘serogroups’. Bacteria can change their serotype through genetic recombination, termed ‘switching’, which can allow strains to evade vaccine-induced immunity
By combining epidemiological data with whole genome sequencing, this work finds a robust and unexpected pattern of serotype switching in a sample of bacteria collected following the introduction of routine anti-pneumococcal vaccination: switching was much more likely to exchange one serotype for another within the same serogroup than expected by chance
Summary
Streptococcus pneumoniae is a human nasopharyngeal commensal bacterium and important respiratory pathogen. Children develop anticapsular antibodies after exposure to the bacterium, evidence for their impact on disease risk is mixed [9] Data indicating this immune response provides protection against nasopharyngeal carriage has been found for only a few serotypes [10,11,12], though mathematical models suggest subtle effects on carriage may exist and help maintain the high level diversity of serotypes observed in pneumococcal populations [13]. Following the introduction of PCV7, a substantial fall in the carriage of the seven vaccine serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) was observed without any substantial overall reduction in the rates of pneumococcal colonisation [16,17] This was primarily the result of an increase in the rate of carriage of non-vaccine type strains, termed ‘serotype replacement’ [18,19,20]. Strains have altered their serotype through the acquisition of a different capsular polysaccharide synthesis (cps) locus via genetic transformation
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