FIG. 6.

Proposed AI-2 signaling with QS regulators LsrR and LsrK. During early and mid-exponential phases, AI-2 levels are low, insufficient for triggering rapid uptake. LsrR binds and represses many genes including lsr genes. As AI-2 accumulates extracellularly, it begins to be transported into the cells via a non-Lsr pathway or otherwise accumulates within the cells (or other pre-AI-2 anomers), which then bind to LsrR and derepress many QS genes including lsrR, flu, wza, and dsrA (crescents represent sRNA). Lsr-mediated AI-2 uptake remains repressed, as its derepression is due to phospho-AI-2. This temporal model is consistent with the activation of QS phenotypes that are switched on in late exponential phase. Finally, when the AI-2 concentration reaches the uptake “threshold” and cells sense nutrient depletion, lsr rapidly imports AI-2. Thereafter, cells phosphorylate the imported AI-2 signal, which results in the cessation of the LsrR/AI-2 regulation and amplification of LsrR/phopho-AI-2 regulation. Hence, a rapid QS switch is manifested by a change in the phosphorylation state of AI-2 and its binding to LsrR.