Colonization dynamics of are determined by polymorphisms in the BlpAB transporter.

Colonization of the human airways, the first step in the pathogenesis of (), 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 strains. Competition both between and within strains is mediated by bacteriocin gene clusters, notably the quorum sensing-regulated bacteriocin-like peptide () locus. A key component of this system is the BlpAB transporter that exports pheromones and bacteriocins expressed by the locus. However, ~75% of 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 mediated by bacterial competition impact host colonization.IMPORTANCE 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 bacteriocins that are exported by the cell through both BlpAB and ComAB transporters. While most 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 . This correlates with longer carriage duration in the human population and a competitive advantage during experimental co-colonization. Our work highlights the reasons behind the persistence of with a functional BlpAB. These findings reveal how genetic variability in the locus shapes colonization and evolutionary success.