Threshold regulation and stochasticity from the MecA/ClpCP proteolytic system inStreptococcus mutanscompetence

Abstract

SummaryMany bacterial species use the MecA/ClpCP proteolytic system to block entry into genetic competence. InStreptococcus mutans, MecA/ClpCP degrades ComX (also called SigX), an alternative sigma factor for thecomYoperon and other late competence genes. Although the mechanism of MecA/ClpCP has been studied in multipleStreptococcusspecies, its role within noisy competence pathways is poorly understood.S. mutanscompetence 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 ofcomYin individualS. mutanscells. Our data show that MecA/ClpCP is active under both XIP and CSP stimulation, that it provides threshold control ofcomY, and that it adds noise incomYexpression. 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 noisycomX, that enhances phenotypic diversity.