Streptococcus mitis bacteriocins drive contact-dependent lysis of S. pneumoniae facilitating transformation in multispecies environments

Natural competence allows bacterial species like Streptococcus pneumoniae and S. mitis to acquire environmental DNA, driving horizontal gene transfer (HGT) and adaptation. In S. pneumoniae , a human pathogen, competence-induced predation is well characterized and involves the release of bacteriocins and a murein hydrolase to lyse noncompetent siblings and liberate DNA. In contrast, in the human commensal S. mitis , mechanisms mediating DNA acquisition remain poorly understood. Here, we identify a diverse set of competence-associated bacteriocins ( cab ) that are produced by S. mitis during the late phase of competence. We focus on one bacteriocin pair, CabAB, that triggers contact-dependent growth inhibition and lysis of S. pneumoniae through activation of the major pneumococcal autolysin LytA. We demonstrate that CabAB compromises S. pneumoniae membrane integrity, leading to formation of intracellular membrane aggregates and the release of cytoplasmatic content, thereby increasing available DNA, which enhances HGT from S. pneumoniae to S. mitis in biofilms. These findings uncover a mechanism of interspecies predation and gene acquisition, revealing a critical role for competence-associated bacteriocins in shaping evolutionary dynamics of streptococci.