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

Chromosomal barcoding and high-throughput sequencing were used to investigate the population dynamics of Streptococcus pneumoniae. During infant mouse colonization, >35-fold reduction in diversity and expansion of a single clonal lineage was observed within 1 day post-inoculation. This loss of diversity was not due to immune factors, host microbiota or exclusively because of genetic drift. Rather, it required the expression of blp bacteriocins induced by the BlpC-quorum sensing pheromone. This points towards the role of intra-strain competition whereby the subpopulation reaching a quorum eliminates others that have yet to activate the blp locus. We show that this loss of diversity also restricts the number of unique clones that could establish colonization during transmission between hosts. Moreover, we show that genetic variation in the blp locus is associated with transmissibility in the human population. We posit this is due to its importance in clonal selection and its role as a selfish element.