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.