BlpC-mediated selfish program leads to rapid loss of Streptococcus pneumoniae clonal diversity during infection

Successful colonization of a host requires bacterial adaptation through genetic and population changes that are incompletely defined. Using chromosomal barcoding and high-throughput sequencing, we investigate the population dynamics of Streptococcus pneumoniae during infant mouse colonization. Within 1 day post inoculation, diversity was reduced >35-fold with expansion of a single clonal lineage. This loss of diver-sity was not due to immune factors, microbiota, or exclusive genetic drift. Rather, bacteriocins induced by the BlpC-quorum sensing pheromone resulted in predation of kin cells. In this intra-strain competition, the sub -population reaching a quorum likely eliminates others that have yet to activate the blp locus. Additionally, this reduced diversity restricts the number of unique clones that establish colonization during transmission be-tween hosts. Genetic variation in the blp locus was also associated with altered transmissibility in a human population, further underscoring the importance of BlpC in clonal selection and its role as a selfish element.