RcrR: A Multifunctional Transcriptional Regulator Orchestrating the cariogenic virulence of Streptococcus mutans

ABSTRACT:

We systematically investigated RcrR's contribution to cariogenic virulence using isogenic wild-type, DeltarcrR deletion mutant, and complemented strains. We assessed bacterial growth, biofilm architecture, acid tolerance, and H+-ATPase activity. To delineate the global regulatory network, we integrated untargeted metabolomics with data-independent acquisition (DIA)-based quantitative proteomics. Deletion of rcrR impaired bacterial growth, resulted in a structurally loose biofilm with significantly reduced water-insoluble extracellular polysaccharides (EPS) and extracellular DNA (eDNA), and markedly downregulated the transcription of glucosyltransferase genes gtfB, gtfC, and gtfD. Under acidic conditions (pH 5.5), the DeltarcrR mutant showed substantially reduced acidogenicity and aciduricity, accompanied by significantly diminished H+-ATPase activity. Multi-omics analyses revealed that rcrR deletion depleted critical glycolytic intermediates, most notably fructose-1,6-bisphosphate (FBP), and broadly suppressed the expression of proteins involved in carbohydrate metabolism, ABC transport systems, and quorum sensing pathways. Our findings demonstrate that RcrR functions as a central regulator coordinating energy metabolism, nutrient transport, and cell signaling to drive the full spectrum of S. mutans cariogenic virulence. This identifies RcrR as a promising molecular target for the development of novel preventive and therapeutic strategies against dental caries

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - negative - hilic

PROVIDER: MTBLS15272 | MetaboLights | 2026-08-06

REPOSITORIES: MetaboLights