GSE110275
Characterization of the trehalose utilization operon in Streptococcus mutans reveals that the TreR transcriptional regulator is involved in stress response pathways and toxin production
Streptococcus mutans, 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 recently been implicated in enhancing the virulence of epidemic strains of the pathogen, Clostridium difficile.  In this study, deletion mutants of all three genes in the putative S. mutans trehalose utilization operon were characterized and 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.  RNAseq of a treR deletion mutant suggested that in S. mutans, TreR acts as a trehalose-sensing activator of transcription of the tre operon, rather than a repressor, as described in other species.  In addition, deletion of treR caused the down-regulation of a number of genes involved in genetic competence and bacteriocin production, supporting results of a recent study linking trehalose and the S. mutans competence pathways.  Finally, deletion of treR compromised the ability of S. mutans to inhibit the growth of the competing species, Streptococcus gordonii and Lactococcus lactis.  Taken together, this study solidifies the role of the S. mutans tre operon in trehalose utilization and suggests novel functions for the TreR regulator, including roles in stress response and competitive fitness. Overall design: Transcriptional profiling was performed using RNA extracted from cultures of S. mutans parent strain UA159 and the ?treR derivative grown in tryptone-yeast extract medium supplemented with either glucose, galactose or trehalose.