Transcriptional regulation of the pneumococcal capsule can dictate serotype-specific infection

Streptococcus pneumoniae (the pneumococcus) is a human bacterial pathogen and the major cause of bacterial pneumonia, which can further develop into sepsis. The pneumococcus has evolved over 107 antigenically-distinct serotypes that are defined by the chemical composition of its capsule; its major virulence factor and the main protective antigen within the vaccine. Owing to its capsule diversification, certain serotypes are known for being more effective at either colonization or invasiveness. It has historically been accepted that these differences are due to the chemical properties of the capsule itself, whose biosynthetic genes are encoded in a single capsular polysaccharide (cps) operon. Here we show that infection outcomes can also be the result of a serotype's subtle, natural variations within the regulatory region which results in unique transcriptional control of the cps locus. We propose that these data explain, in part, how this pathogen might rapidly evolve its capsule expression to accommodate evolutionary pressures introduced from pneumococcal vaccines, without having to rely on genetic recombination.