RESEARCH ARTICLE Selective and Genetic Constraints on Pneumococcal Serotype

Streptococcus pneumoniae isolates typically express one of over 90 immunologically dis-tinguishable 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 be-tween-serogroup switches all spanned the entire cps locus, some of those that caused with-in-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 link-age 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 ge