Serotype-Dependent Effects on the Dynamics of Pneumococcal Colonization and Implications for Transmission

ABSTRACT

Capsule-switch mutants were compared to analyze how serotype affects the success of Streptococcus pneumoniae (Spn) during colonization and transmission. Strains of multiple serotypes were tested in highly susceptible infant mice, both singly and in competitive assays. Our findings demonstrated a role of serotype, apart from genetic background, in competitive success of strains, but this depended on timing postinoculation. As is the case for natural carriage, there was a hierarchy of success among serotypes using capsule-switch strains. The long-term dominance of a serotype was established within the first 4 h after acquisition, suggesting an effect independent of Spn-induced host responses. The hierarchy of serotype dominance correlated with decreased clearance rather than increased growth in vivo. Competitive assays staggering the timing of challenge showed that the first strain to dominate the niche sustained its competitive advantage, potentially explaining how increased density from delayed early clearance could result in serotype-dependent success. Effector molecules of intrastrain competition (fratricide), regulated by the competence operon in a quorum-sensing mechanism, were required for early niche dominance. This suggested a winner-takes-all scenario in which serotype is a major factor in achieving early niche dominance, such that once a strain reaches a threshold density it is able to exclude competitors through fratricide. Serotype was also an important determinant of transmission dynamics, although transit to a recipient host depended on effects of serotype different from its contribution to the dominance of colonization in the donor host.