Fig. 7.

Working model for glucose and oxygen-dependent regulation of the S. mutans Cid/Lrg system. Lrg and Cid activities are regulated in a growth-phase-dependent fashion by oxygen and glucose levels, which would change dramatically as cells progress from early exponential to stationary phase. As cells actively grow (high levels of oxygen and glucose available), cid expression is dominant but lrg is minimal and probably under the control of CcpA. As cells enter stationary phase (oxygen/glucose-limited cells), lrg expression is dramatically increased by the LytST TCS. In contrast, cid expression is gradually diminished, in part due to CcpA-dependent regulation. The expression level of lrg and cid seems to be tightly balanced throughout growth, and direct interactions between Lrg and Cid proteins may be involved in achieving this balance. Therefore, by sensing multiple environmental inputs and modulating the balance between Lrg and Cid, S. mutans is able to modulate growth and biofilm formation, which are critical for virulence expression by this pathogen.