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. ImportanceMany streptococci are naturally competent, acquiring environmental DNA through transformation. This includes pathogens like S. pneumoniae and commensals like S. mitis, which can exchange genetic material through horizontal gene transfer (HGT). For example, S. mitis can acquire pneumococcal capsules, leading to its misidentification in polymicrobial samples such as those obtained from the upper respiratory tract. Understanding the drivers of HGT between these species is therefore critical. Here, we characterize a competence-induced bacteriocin cluster in S. mitis. These bacteriocins lyse pneumococci, promoting DNA release and enhancing gene transfer in dual-species biofilms. Our findings uncover a mechanism by which competence-associated predation promotes interspecies HGT, shaping the evolution and epidemiology of streptococcal populations.