Biology subjects

Damoczi, J.

Publications and source records attributed to Damoczi, J..

2 recordsLinked to original sources

bioRxiv2026

A streamlined ABC extruder-repressor module drives multi-bacteriocin resistance in streptococci

Bacteria inhabiting competitive microbial environments must rapidly detect and neutralize antimicrobial peptides (AMPs) produced by rivals. The activation of defense pathways relies on dedicated sensors and complex regulatory cascades. Here, we uncover a streamlined, membrane-embedded mechanism in Gram-positive bacteria that directly links detection to transcriptional control. We show that a YtrA-family transcriptional repressor is regulated through an unconventional direct physical interaction with its cognate ABC transporter. In Streptococcus salivarius, the MbrAB efflux pump sequesters the YtrA-like repressor MbrR through a competitive binding mechanism. Upon bacteriocin sensing, MbrR shifts from promoter-proximal DNA repression sites to membrane-associated sequestration via interaction with MbrA, thereby activating the bacteriocin defense system. ATP binding by MbrA facilitates MbrR recruitment, whereas ATP hydrolysis promotes its release, providing a dynamic, flux-responsive feedback loop finely tuned to environmental threat. Structural modeling, synteny, and conservation analyses reveal that this transporter-mediated sequestration mechanism is highly conserved across Gram-positive bacteria, suggesting a widespread and efficient strategy for AMP resistance that bypasses the need for classical sensor kinases. These findings expand the known repertoire of bacterial sensing and resistance systems and provide new insight into how Gram-positive bacteria swiftly adapt to interbacterial antagonism. IMPORTANCEBacteria in crowded microbial communities face constant chemical warfare, yet how they sense and counteract antimicrobial peptides (AMPs) remains incompletely understood. Here we uncover a minimalist sensing-response module in streptococci in which YtrA-family transcriptional repressors are directly regulated by their partner ABC transporters. In Streptococcus salivarius, the MbrAB transporter detects incoming bacteriocins and physically sequesters the MbrR repressor, triggering rapid induction of a multi-gene defense program. ATP binding drives MbrR capture, while hydrolysis resets the system, providing a fast, energy-coupled switch that bypasses canonical two-component signaling. Comparative genomics shows that this transporter-repressor circuit is highly conserved across Bacillota, pointing to a broadly distributed and efficient strategy for AMP resistance. These findings reveal a direct physical link between membrane transport and transcriptional control, redefining how Gram-positive bacteria can sense and respond to microbial threats. ONE SENTENCE SUMMARYWe identify a conserved transporter-repressor module in streptococci that directly couples bacteriocin detection to transcriptional activation, revealing a minimalist and rapid mechanism for antimicrobial peptide resistance.

microbiology↗

bioRxiv2024

Uncovering the class II-bacteriocin predatiome in salivarius streptococci

Facing the surge of antibiotic resistance, the medical field has a critical need for alternatives to treat bacterial infections. Among these, the use of bacteriocins, ribosomally-synthesized antimicrobial peptides produced by bacteria, is considered to be a promising route. In the human commensal Streptococcus salivarius, the production of unmodified class II bacteriocins is directly controlled at the transcriptional level by the quorum-sensing ComRS system. Here, we used an integrated approach combining bioinformatics and synthetic biology to identify novel bacteriocins from salivarius streptococci active against human pathogens. We developed a bioinformatic pipeline that combines conservation of DNA motifs for genetic regulation and features of bacteriocin primary sequences to uncover cryptic class II bacteriocins. Notably, we discovered more than 50 novel bacteriocin candidates clustered into 21 groups from 100 genomes of S. salivarius. Strain-based analysis of bacteriocin cocktails revealed an important diversity restricted to seven distinct loci, probably resulting from bacteriocin intra- and inter- species exchanges. Using in vitro or in vivo production and synthetic biology tools, we showed that most of them are active against a panel of Gram-positive bacteria, including clinically- relevant pathogens. Overall, this work provides a new search-to-test generic pipeline for the discovery of novel bacteriocins in Gram-positive bacteria that could be used in cocktails for broad applications in the food and biomedical fields. IMPORTANCETo survive in highly challenging environments, streptococci have evolved a competence- predation coupling mechanism for genome plasticity. This developmental process is highly regulated at the transcriptional level, masking the predation killing effects in usual laboratory conditions. Here, we present a general strategy that combines bioinformatics and synthetic biology to unveil class II bacteriocins in streptococci. Its implementation to the beneficial species Streptococcus salivarius revealed around 40 class II salivaricin cocktails explained by the plasticity of seven independent loci. Notably, the salivaricin predatiome includes a subtle blend of fratricins, sobrinicins, and broad-spectrum bacteriocins with overlapping activities against a wide spectrum of low-GC Gram-positive bacteria, including notorious pathogens. Furthermore, most of those bacteriocins are predicted to be variants of a common -hairpin structure, indicating that their mode of action evolved convergently. Finally, the discovery of ca. 50 novel bacteriocins offers perspectives for the rational assembly of potent cocktails active against pathogenic staphylococci, streptococci or enterococci.

microbiology↗