TY - JOUR
T1 - Quorum-sensing crosstalk-driven synthetic circuits
T2 - From Unimodality to trimodality
AU - Wu, Fuqing
AU - Menn, David J.
AU - Wang, Xiao
N1 - Funding Information:
We thank Jeff Hasty for the microfluidic setup and chip design. We also thank Riqi Su and Philippe Faucon for helpful discussions and suggestions. D.J.M. is partially supported by ASU IRA Fulton School of Engineering’s Dean’s fellowship. This study was financially supported by National Science Foundation grant DMS-1100309, American Heart Association grant 11BGIA7440101, and NIH grant GM106081 (to X.W.).
Publisher Copyright:
©2014 Elsevier Ltd. All rights reserved.
PY - 2014/12/18
Y1 - 2014/12/18
N2 - Summary Widespread quorum-sensing (QS) enables bacteria to communicate and plays a critical role in controlling bacterial virulence. However, effects of promiscuous QS crosstalk and its implications for gene regulation and cell decision-making remain largely unknown. Here we systematically studied the crosstalk between LuxR/I and LasR/I systems and found that QS crosstalk can be dissected into signal crosstalk and promoter crosstalk. Further investigations using synthetic positive feedback circuits revealed that signal crosstalk significantly decreases a circuit's bistable potential while maintaining unimodality. Promoter crosstalk, however, reproducibly generates complex trimodal responses resulting from noise-induced state transitions and host-circuit interactions. A mathematical model that integrates the circuit's nonlinearity, stochasticity, and host-circuit interactions was developed, and its predictions of conditions for trimodality were verified experimentally. Combining synthetic biology and mathematical modeling, this work sheds light on the complex behaviors emerging from QS crosstalk, which could be exploited for therapeutics and biotechnology.
AB - Summary Widespread quorum-sensing (QS) enables bacteria to communicate and plays a critical role in controlling bacterial virulence. However, effects of promiscuous QS crosstalk and its implications for gene regulation and cell decision-making remain largely unknown. Here we systematically studied the crosstalk between LuxR/I and LasR/I systems and found that QS crosstalk can be dissected into signal crosstalk and promoter crosstalk. Further investigations using synthetic positive feedback circuits revealed that signal crosstalk significantly decreases a circuit's bistable potential while maintaining unimodality. Promoter crosstalk, however, reproducibly generates complex trimodal responses resulting from noise-induced state transitions and host-circuit interactions. A mathematical model that integrates the circuit's nonlinearity, stochasticity, and host-circuit interactions was developed, and its predictions of conditions for trimodality were verified experimentally. Combining synthetic biology and mathematical modeling, this work sheds light on the complex behaviors emerging from QS crosstalk, which could be exploited for therapeutics and biotechnology.
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U2 - 10.1016/j.chembiol.2014.10.008
DO - 10.1016/j.chembiol.2014.10.008
M3 - Article
C2 - 25455858
AN - SCOPUS:84919952401
VL - 21
SP - 1629
EP - 1638
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 12
ER -