Characterization of the Trehalose Utilization Operon in Streptococcus mutans Reveals that the TreR Transcriptional Regulator Is Involved in Stress Response Pathways and Toxin Production.

, the organism most frequently associated with the development of dental caries, is able to utilize a diverse array of carbohydrates for energy metabolism. One such molecule is trehalose, a disaccharide common in human foods, which has been recently implicated in enhancing the virulence of epidemic strains of the pathogen In this study, mutants with deletions of all three genes in the putative trehalose utilization operon were characterized, and the genes were shown to be required for wild-type levels of growth when trehalose was the only carbohydrate source provided. Interestingly, the TreR transcriptional regulator appeared to be critical for responding to oxidative stress and for mounting a protective stress tolerance response following growth at moderately acidic pH. mRNA sequencing (RNA-seq) of a deletion mutant suggested that in , TreR acts as a trehalose-sensing activator of transcription of the operon, rather than as a repressor, as described in other species. In addition, deletion of caused the downregulation of a number of genes involved in genetic competence and bacteriocin production, supporting the results of a recent study linking trehalose and the competence pathways. Finally, deletion of compromised the ability of to inhibit the growth of the competing species and Taking the results together, this study solidifies the role of the operon in trehalose utilization and suggests novel functions for the TreR regulator, including roles in the stress response and competitive fitness. is the primary etiologic agent of dental caries, which globally is the most common chronic disease. must be able to outcompete commensal organisms in its dental plaque niche in order to establish persistence and pathogenesis. To that end, metabolizes a diverse array of carbohydrates to generate acid and impede its acid-sensitive neighbors. Additionally, utilizes quorum signaling through genetic competence-associated pathways to induce production of toxins to kill its rivals. This study definitively shows that the trehalose utilization operon is required for growth in trehalose. Furthermore, this study suggests that the TreR transcriptional regulator has a novel role in virulence through regulation of genes involved in genetic competence and toxin production.