Streptolancidin D mediates intra-species competition in Streptococcus pneumoniae through the Rgg₁₄₄/SHP₁₄₄ quorum-sensing system

Streptococcus pneumoniae is a major colonizer of the human nasopharynx, where inter- and intra-strain competition plays a critical role in shaping population structure and influencing vaccine outcomes. Bacteriocins are key mediators of intra-species competition, yet many of their functions and regulatory mechanisms remain poorly understood. Here, we identify and characterize streptolancidin D, a previously uncharacterized bacteriocin encoded by the sldA-T locus and demonstrate its contribution to pneumococcal competition. Using a naturally colonizing strain, we show that deletion of sldA-T impairs inhibition of competitor strains in in vitro biofilms and during murine co-colonization. We further show that sldA-T is regulated by the Rgg 144 /SHP 144 quorum sensing system, with promoter activity abolished in a SHP-deficient background and partially restored by exogenous peptide stimulation. Genomic analyses revealed that sldA-T is consistently encoded downstream of the Rgg 144 /SHP 144 system and is present in ~12% of over 7,500 pneumococcal genomes, with lineage-specific patterns of distribution. This observation suggests a regulated mechanism that provides competitive advantages in strain–strain interactions, which might help explaining the long-term persistence of certain clones even under PCV13 pressure. Our findings uncover a previously unrecognized quorum sensing-regulated antimicrobial system in S. pneumoniae that enhances strain competitiveness and may contribute to lineage persistence and replacement dynamics under selective pressures such as vaccination.