A ComRS competence pathway in the oral pathogen Streptococcus sobrinus

Abstract

Streptococcus sobrinus is one of two species of bacteria that cause dental caries (tooth decay) in humans. Our knowledge of S. sobrinus is limited despite the organism's important role in oral health. It is widely believed that S. sobrinus lacks the natural competence pathways that are used by other streptococci to regulate growth, virulence, and quorum sensing. The lack of natural competence has also prevented genetic manipulation of S. sobrinus, limiting our knowledge of its pathogenicity.We discovered a functional ComRS competence system in S. sobrinus. The ComRS pathway in S. sobrinus has a unique structure, including two copies of the transcriptional regulator ComR and a peptide pheromone (XIP) that lacks aromatic amino acids. We show that synthetic XIP allows transformation of S. sobrinus with plasmid or linear DNA, and we leverage this newfound genetic tractability to confirm that only one of the ComR homologs is required for induced competence.Although S. sobrinus is typically placed among the mutans group streptococci, the S. sobrinus ComRS system is structurally and functionally similar to the competence pathways in the salivarius group. Like S. salivarius, the ComRS gene cluster in S. sobrinus includes a peptide cleavage/export gene, and the ComRS system appears coupled to a bacteriocin response system. These findings raise questions about the true phylogenetic placement of S. sobrinus.Finally, we identified two strains of S. sobrinus appear to be "cheaters" by either not responding to or not producing XIP. While the mechanisms of cheating could be independent, we show how a recombination event in the non-responsive strain would restore function of the ComRS pathway but delete the gene encoding XIP. Thus the S. sobrinus ComRS pathway provides a lens into the evolution of ecological cheaters.