Figure 5.

Natural and synthetic feedback loops in QS. (A) A simple topology for a functional communication network. The AHL signal is produced constitutively by LuxI and is received by LuxR, which may activate downstream genes. LuxR activity shows a simple saturating increase with time, as cells proliferate and AHL accumulates. This design was used successfully in early synthetic QS networks (You et al. 2004; Basu et al. 2005). (B) Positive feedback slows response time and improves response fidelity. With LuxI expression under the control of LuxR, the increase in LuxR activity with time becomes slower and more concave. Note the relatively flat response for early time points with low AHL levels, reflecting insensitivity to transient induction. The dotted line indicates the time required for half-maximal LuxR activity, which is extended in this case. Natural QS systems widely employ this kind of positive feedback, and it has been useful in synthetic systems as well (Brenner et al. 2007). (C) Negative feedback and temporal control. By introducing AiiA, which degrades AHL, under the control of LuxR, Danino et al. (2010) produced cells that respond to a quorum by destroying the QS signal. The result was synchronized, population-level oscillations in QS activity. Negative feedback is also a feature in many natural QS systems, where it may provide fine temporal response control.