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Purification of a High Molecular Mass Protein in Streptococcus mutans
Published on: September 14, 2019
Threshold regulation and stochasticity from the MecA/ClpCP proteolytic system in Streptococcus mutans competence
1Department of Physics, University of Florida, Gainesville, FL 32611, USA.
Abstract:
Many bacterial species use the MecA/ClpCP proteolytic system to block entry into genetic competence. In Streptococcus mutans, MecA/ClpCP degrades ComX (also called SigX), an alternative sigma factor for the comY operon and other late competence genes. Although the mechanism of MecA/ClpCP has been studied in multiple Streptococcus species, its role within noisy competence pathways is poorly understood. S. mutans competence can be triggered by two different peptides, CSP and XIP, but it is not known whether MecA/ClpCP acts similarly for both stimuli, how it affects competence heterogeneity, and how its regulation is overcome. We have studied the effect of MecA/ClpCP on the activation of comY in individual S. mutans cells. Our data show that MecA/ClpCP is active under both XIP and CSP stimulation, that it provides threshold control of comY, and that it adds noise in comY expression. Our data agree quantitatively with a model in which MecA/ClpCP prevents adventitious entry into competence by sequestering or intercepting low levels of ComX. Competence is permitted when ComX levels exceed a threshold, but cell-to-cell heterogeneity in MecA levels creates variability in that threshold. Therefore, MecA/ClpCP provides a stochastic switch, located downstream of the already noisy comX, that enhances phenotypic diversity.
Insights
The MecA/ClpCP system in Streptococcus mutans controls genetic competence by degrading ComX (competence regulatory protein). This system acts as a stochastic switch, enhancing cell-to-cell variability in competence pathways.
Area of Science:
- Microbiology
- Bacterial genetics
- Molecular biology
Background:
- Many bacteria utilize the MecA/ClpCP proteolytic system to regulate entry into genetic competence.
- In Streptococcus mutans, this system degrades ComX (alternative sigma factor), impacting competence gene expression.
- The precise role of MecA/ClpCP in the inherently variable competence pathways of S. mutans remains unclear.
Purpose of the Study:
- To investigate the function of the MecA/ClpCP system in individual Streptococcus mutans cells during competence activation.
- To determine if MecA/ClpCP acts similarly under different competence-stimulating peptides (CSP and XIP).
- To elucidate how MecA/ClpCP influences competence heterogeneity and how its regulation is overcome.
Main Methods:
- Single-cell analysis of comY activation in Streptococcus mutans.
- Quantitative modeling to simulate MecA/ClpCP activity and ComX sequestration.
- Investigating the impact of MecA/ClpCP on competence pathway noise and threshold control.
Main Results:
- Meca/ClpCP is active under both XIP and CSP stimulation, demonstrating conserved function.
- The MecA/ClpCP system imposes threshold control on comY expression.
- Cell-to-cell heterogeneity in MecA levels introduces variability, acting as a stochastic switch that enhances phenotypic diversity.
Conclusions:
- Meca/ClpCP functions as a crucial regulator, preventing premature competence by controlling ComX levels.
- The system's inherent variability in MecA levels contributes significantly to phenotypic diversity in bacterial competence.
- This stochastic switching mechanism enhances bacterial adaptability and survival in fluctuating environments.
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