# Colonization dynamics of Streptococcus pneumoniae are determined by polymorphisms in the BlpAB transporter

## TL;DR

This study shows that Streptococcus pneumoniae strains with a functional BlpAB transporter colonize human airways longer and compete better, explaining why this transporter persists despite being redundant.

## Contribution

The study identifies the evolutionary advantage of BlpAB(+) Streptococcus pneumoniae strains through their impact on colonization dynamics and competitive success.

## Key findings

- BlpAB(+) strains exhibit slower loss of clonal diversity during colonization in mice.
- BlpAB(+) strains have a median carriage duration ~177 days longer in human populations.
- Functional BlpAB provides a competitive advantage during co-colonization experiments.

## Abstract

Colonization of the human airways, the first step in the pathogenesis of Streptococcus pneumoniae (Spn), 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 Spn strains. Competition both between and within strains is mediated by bacteriocin gene clusters, notably the quorum sensing-regulated bacteriocin-like peptide (blp) locus. A key component of this system is the BlpAB transporter that exports pheromones and bacteriocins expressed by the blp locus. However, ~75% of Spn 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 Spn mediated by bacterial competition impact host colonization.

Spn 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 blp bacteriocins that are exported by the cell through both BlpAB and ComAB transporters. While most Spn 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 in vivo. This correlates with longer Spn carriage duration in the human population and a competitive advantage during experimental co-colonization. Our work highlights the reasons behind the persistence of Spn with a functional BlpAB. These findings reveal how genetic variability in the blp locus shapes Spn colonization and evolutionary success.