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Regulation of cid and lrg expression by CodY in Streptococcus mutans
Sang-Joon Ahn1, Hey-Min Kim1, Shailja Desai1
1Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA.
Microbiologyopen
|April 14, 2020
Summary
The global regulator CodY directly controls Streptococcus mutans cid and lrg operons. CodY, along with CcpA, coordinates pyruvate metabolism in response to environmental and cellular conditions.
Area of Science:
- Microbiology
- Molecular Biology
- Bacterial Pathogenesis
Background:
- Streptococcus mutans persistence in adverse environments is key to its cariogenicity.
- The S. mutans Cid/Lrg system integrates environmental signals, modulating virulence and homeostasis.
- Cid/Lrg expression is linked to metabolic pathways influenced by growth phase and nutrient availability.
Purpose of the Study:
- To investigate the direct role of the global transcriptional regulator CodY in controlling cid and lrg operon expression in S. mutans.
- To elucidate the interaction between CodY, CcpA, and metabolic pathways, specifically pyruvate flux and utilization.
Main Methods:
- Bioinformatic analysis of conserved CodY-binding motifs in cid and lrg promoter regions.
- Electrophoretic mobility shift assays (EMSAs) and promoter reporter assays to confirm CodY-DNA interactions.
- DNase I footprinting to precisely map CodY binding sites.
- Genetic manipulation (overexpression and deficiency) of CodY and LytST, and assessment of lrgAB expression.
- Analysis of CodY and CcpA involvement in pyruvate metabolism.
Main Results:
- CodY directly binds to and regulates the expression of the cid and lrg operons in S. mutans.
- CodY binding sites were identified and confirmed in both promoter regions.
- CodY is necessary for the full regulation of lrgAB by LytST.
- Both CodY and CcpA play roles in regulating pyruvate flux and utilization.
Conclusions:
- CodY is a direct transcriptional regulator of the cid and lrg operons in S. mutans.
- CodY, in conjunction with CcpA, contributes to the coordination of pyruvate uptake and utilization.
- These regulatory mechanisms allow S. mutans to adapt its metabolism based on environmental and cellular cues.
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