Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1629-1638 |
| Number of pages | 10 |
| Journal | Chemistry and Biology |
| Volume | 21 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 18 2014 |
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ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Molecular Biology
- Clinical Biochemistry
- Molecular Medicine
- Pharmacology
Cite this
Quorum-sensing crosstalk-driven synthetic circuits : From Unimodality to trimodality. / Wu, Fuqing; Menn, David J.; Wang, Xiao.
In: Chemistry and Biology, Vol. 21, No. 12, 18.12.2014, p. 1629-1638.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Quorum-sensing crosstalk-driven synthetic circuits
T2 - From Unimodality to trimodality
AU - Wu, Fuqing
AU - Menn, David J.
AU - Wang, Xiao
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 -