Biology subjects

Lanca, J.

Publications and source records attributed to Lanca, J..

3 recordsLinked to original sources

bioRxiv2026

Serotype-independent inhibition of S. pneumoniae by SMiTE, a commensal-derived bacteriocin

Streptococcus pneumoniae remains a leading cause of disease despite widespread vaccination, highlighting the need for serotype-independent strategies. We recently identified commensal streptococci that produce bacteriocins with anti-pneumococcal activity. Here, we evaluate these bacteriocins as candidates for pneumococcal control. Using cell-free protein synthesis, we screened 58 bacteriocins, the majority of which absent in available pneumococcal genomes, and identified SMiTE as the most potent. Purified SMiTE disrupted pneumococcal membrane integrity, as shown by confocal, transmission, and scanning electron microscopy, induced ATP leakage, and triggered transcriptional responses consistent with envelope stress and metabolic remodeling. In a mouse nasopharyngeal colonization model, intranasal SMiTE treatments reduced pneumococcal loads by 65-fold with no significant weight loss. SMiTE inhibited a broad range of serotypes, with strongest activity against serotype 3, which is poorly controlled by current vaccines, while sparing most oral and upper respiratory tract commensals. Repeated sub-inhibitory exposure did not select resistant mutants in line with the membrane-targeting mechanism. These findings establish SMiTE as a commensal-derived strategy for serotype-independent, microbiota-sparing pneumococcal decolonization.

microbiology↗

bioRxiv2025

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.

microbiology↗

bioRxiv2025

Bacteriocin-mediated prevention of secondary pneumococcal pneumonia by a human commensal Streptococcus mitis strain

Streptococcus pneumoniae remains a major public health threat despite widespread use of vaccines and antibiotics. Its well-established synergy with influenza A virus (IAV) often results in secondary bacterial pneumonia, a condition associated with high morbidity and mortality. As pneumococcal pneumonia is invariably preceded by nasopharyngeal colonization, preventing colonization represents a promising intervention strategy. Current approaches, including pneumococcal conjugate vaccines and antibiotics, can drive serotype replacement and antimicrobial resistance, underscoring the need for novel, targeted, and serotype-independent alternatives. We previously identified seven commensal streptococcal strains (S. oralis A22 and S. mitis B22-G22) that robustly inhibit S. pneumoniae growth and biofilm formation in vitro. Here, using a murine model, we demonstrate that colonization with the commensal strain F22Ad significantly reduces pneumococcal density in the nasopharynx by day 10 post-infection and prevents pneumococcal dissemination to the lungs following IAV co-infection. This protective effect was dependent on bacteriocins encoded at the blp1 locus. Among these, Bac2v1 (alone or in combination with Bac1) significantly reduced pneumococcal colonization. Notably, Bac2v1 exerted serotype-independent inhibitory activity, impairing the growth of diverse pneumococcal strains. Our findings provide the first in vivo proof-of-concept that commensal streptococci, and specifically their bacteriocins, can disrupt S. pneumoniae colonization and prevent progression to secondary bacterial pneumonia. This work introduces a previously unrecognized precision-based approach to pneumococcal disease prevention, offering a potential complement to current strategies.

microbiology↗