Abstract
Competition among microorganisms is a key determinant of successful host colonization and persistence. For Streptococcus pneumoniae, lower than predicted rates of co-colonizing strains suggest a competitive advantage for resident bacteria over newcomers. In light of evolutionary theory, we hypothesized that S. pneumoniae use owner-intruder asymmetries to settle contests, leading to the disproportionate success of the initial resident 'owner', regardless of the genetic identity of the 'intruder'. We investigated the determinants of within-host competitive success utilizing S. pneumoniae colonization of the upper respiratory tract of infant mice. Within 6 h, colonization by the resident inhibited colonization by an isogenic challenger. The competitive advantage of the resident was dependent on quorum sensing via the competence (Com) regulon and downstream choline binding protein D (CbpD) and on the competence-induced bacteriocins A and B (CibAB) implicated in fratricide. CbpD and CibAB are highly conserved across pneumococcal lineages, indicating evolutionary advantages for asymmetric competitive strategies within the species. Mathematical modelling supported a significant role for quorum sensing via the Com regulon in competition, even for strains with different competitive advantages. Our study suggests that asymmetric owner-intruder competitive strategies do not require complex cognition and are used by a major human pathogen to determine 'ownership' of human hosts.