Metabolic Regulation in Cariogenic Bacteria

The capacity of Streptococcus mutans and related oral streptococci to regulate carbohydrate uptake and processing underlies their role in dental plaque dysbiosis and caries development. These organisms employ an intricate network of sugar transport systems, notably phosphotransferase system permeases and ABC transporters, to import mono- and disaccharides. Once internalised, substrates are channelled into glycolysis, generating ATP and lactic acid that acidify the biofilm microenvironment. Central metabolic regulators such as CcpA and CodY integrate signals from carbohydrate availability and (p)ppGpp-mediated stringent response to coordinate expression of genes involved in glycolysis, amino acid synthesis and stress tolerance mechanisms. Two-component systems including LytST and the Cid/Lrg holin–antiholin analogues modulate pyruvate flux and cell death–lysis processes, further shaping biofilm architecture and aciduricity. Metabolic cross-talk with stress-response pathways enhances survival under low-pH and oxidative conditions, while feedback loops in sugar catabolism fine-tune virulence traits such as extracellular polysaccharide production, acid tolerance and interspecies competition. Recent advances have begun to unravel how dynamic proteome remodelling and global transcriptional regulators synchronise metabolic homeostasis, presenting new avenues for targeted disruption of cariogenic pathways. Ongoing research emphasises the importance of metabolic flexibility as a determinant of pathogenic potential and highlights practical strategies to mitigate caries by modulating oral microbial metabolism.

Research from Nature Portfolio

Proteomic analyses leveraging label-free quantitative mass spectrometry have mapped the stress-induced proteome remodelling in mutants lacking LrgAB, revealing coordinated changes across amino acid biosynthesis, central carbon metabolism, transporters and regulatory proteins. Such studies illustrate how the Cid/Lrg system governs pyruvate uptake and energy flux during stationary phase and under oxidative, heat and antibiotic stress. Notably, disruptions in LrgAB alter the abundance of key enzymes in glycolysis and the tricarboxylic acid cycle, underscoring its central role in maintaining metabolic homeostasis and aciduricity. These findings establish a mechanistic link between membrane-associated holin–antiholin analogues and global metabolic regulation, offering a foundation for interventions aimed at destabilising cariogenic biofilms through targeted metabolic interference.

Metabolic Regulation in Cariogenic Bacteria publication trend

The graph below shows the total number of articles in metabolic regulation in cariogenic bacteria across all publications each year (not limited to Nature Index journals).

Technical terms

Glycolysis: The metabolic pathway converting glucose to pyruvate, yielding ATP and NADH.

Phosphotransferase system (PTS): A multicomponent sugar uptake system that phosphorylates sugars during transport into the cell.

CRISPR-Cas system: An adaptive immune mechanism in bacteria involving clustered regularly interspaced short palindromic repeats and Cas proteins to target foreign nucleic acids.

CcpA: A catabolite control protein that regulates carbon metabolism by binding to DNA in response to carbohydrate availability.

CodY: A global regulator that senses nutrient status via (p)ppGpp and branched-chain amino acids to control gene expression.

Proteomics: The large-scale study of the entire protein complement of a cell, tissue or organism under specific conditions.

LrgAB system: Membrane proteins analogous to holin–antiholin that modulate pyruvate uptake, cell death and biofilm formation.

References

1. Fructose activates a stress response shared by methylglyoxal and hydrogen peroxide in Streptococcus mutans. mBio (2025).
2. CcpA and CodY Regulate CRISPR-Cas System of Streptococcus mutans. Microbiology Spectrum (2023).
3. Identification of the Streptococcus mutans LytST two-component regulon reveals its contribution to oxidative stress tolerance. BMC Microbiology (2012).
4. Characterization of LrgAB as a stationary phase-specific pyruvate uptake system in Streptococcus mutans. BMC Microbiology (2019).
5. Remodeling of the Streptococcus mutans proteome in response to LrgAB and external stresses. Scientific Reports (2017).