The Quorum Sensing-Controlled Competence Regulon Drives H₂O₂ Production in Streptococcus gordonii

Streptococcus gordonii sp. firmicutes is an early colonizer of the oral microbiome and contributes positively to oral health. While this species has been found to produce hydrogen peroxide by spxB expression, the relationship of this expression to the competence regulon has not yet been explored. To this end, this study sought to investigate the connection of the S. gordonii competence regulon quorum sensing (QS) circuitry with downstream proliferative phenotypic expression resulting from competence-stimulating peptide (CSP) exposure, with specific attention to peroxide formation. Following confirmation of the native CSP, RNA-seq was completed to gain insights into transcriptomic variations resulting from CSP incubation. Later, structure-activity relationship (SAR) analyses of the native CSP were completed. The results revealed residues integral to CSP:ComD binding and activation, while indicating which residues were considered dispensable to this process. Phenotypic assessment revealed that peroxide formation was modulated via the competence regulon. Finally, interspecies competition assays were carried out to understand the interactions between S. gordonii and S. mutans, with S. gordonii demonstrating a profound capability of antagonizing S. mutans growth and proliferation. Our results support that this antagonism is mainly attributed to hydrogen peroxide production by S. gordonii. This finding suggests that S. gordonii may be exploited for its beneficial proliferative phenotypes downstream of the competence regulon.