Colonization dynamics of <i>Streptococcus pneumoniae</i> are determined by polymorphisms in the BlpAB transporter

Colonization of the human airways, the first step in the pathogenesis of <i>Streptococcus pneumoniae</i> (<i>Spn</i>), is the determining factor in the ecological spread of the bacterium. Since co-colonization by multiple strains is common, within-host bacterial competition contributes to the success of <i>Spn</i> strains. Competition both between and within strains is mediated by bacteriocin gene clusters, notably the quorum sensing-regulated bacteriocin-like peptide (<i>blp</i>) locus. A key component of this system is the BlpAB transporter that exports pheromones and bacteriocins expressed by the <i>blp</i> locus. However, ~75% of <i>Spn</i> strains lack a functional BlpAB transporter and instead rely on the paralogous ComAB transporter for this export, raising questions about the evolutionary persistence of BlpAB(+) strains. Using molecular barcoding, we demonstrate that BlpAB(+) and BlpAB(-) strains show major differences in population dynamics during colonization modeled in mice. The BlpAB(+) strains exhibit slower loss of clonal diversity as a consequence of intrastrain competition relative to their isogenic BlpAB(-). The contribution of a functional BlpAB transporter was then examined in an association study of >2,000 human carriage isolates from a highly colonized population. The median carriage duration was ~177 days longer for BlpAB(+) relative to BlpAB(-) strains. This increased duration of natural carriage correlates with a competitive advantage for BlpAB(+) strains when tested in the murine model. Thus, our work provides insight into how differences in the population dynamics of <i>Spn</i> mediated by bacterial competition impact host colonization.IMPORTANCE<i>Spn</i> is a frequent colonizer of the human upper respiratory tract. Success during colonization is dictated by the arsenal of weapons these bacteria possess, which provides them with an advantage over their competitors. A key example includes the <i>blp</i> bacteriocins that are exported by the cell through both BlpAB and ComAB transporters. While most <i>Spn</i> strains lack a functional BlpAB, a subset of the strains retains it. Given this redundancy in export systems, our study questioned the evolutionary advantage of retaining BlpAB. Herein, we show that a functional BlpAB transporter causes a slower loss of clonal diversity <i>in vivo</i>. This correlates with longer <i>Spn</i> carriage duration in the human population and a competitive advantage during experimental co-colonization. Our work highlights the reasons behind the persistence of <i>Spn</i> with a functional BlpAB. These findings reveal how genetic variability in the <i>blp</i> locus shapes <i>Spn</i> colonization and evolutionary success.