mBio (Apr 2022)
Serotype-Dependent Effects on the Dynamics of Pneumococcal Colonization and Implications for Transmission
Abstract
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. IMPORTANCE Capsule is the major virulence factor and surface antigen of the opportunistic respiratory pathogen Streptococcus pneumoniae (Spn). Strains of Spn express at least 100 structurally and immunologically distinct types (serotypes) of capsule, but for unknown reasons only a few are common. The effect of serotypes during the commensal interactions of Spn and its host, colonization and transmission, was tested. This was carried out by comparing genetically modified strains differing only in serotype in infant mouse models. Results show that serotype is an important factor in a strain’s success during colonization. This was attributed to the effect of serotype on early clearance of the organism in the host. Competitive factors expressed by Spn (in a mechanism referred to as fratricide) allow the strain gaining this initial advantage to then dominate the upper respiratory tract niche. Serotype also plays an important role in a strain’s success during transmission from one host to another.
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