Bistability and oscillations in co-repressive synthetic microbial consortia.
Bistability and oscillations in co-repressive synthetic microbial consortia.
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DOI：
10.1007/s40484-017-0100-y
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Bennett MR
中科院分区：
文献类型：
--
作者：
Sadeghpour M;Veliz-Cuba A;Orosz G;Josić K;Bennett MR
合成微生物联合体是多种基因工程微生物的集合体，它们被编程为协同产生种群水平的表型。通过协调它们的活动，组成菌株可以表现出难以改造成等基因种群的紧急行为。为了做到这一点，菌株被设计成通过细胞间信号通路相互通信。因此，控制整个种群中基因转录的调控网络对信号分子的胞外浓度很敏感，因此对组成菌株的相对密度也很敏感。在这里，我们使用计算模型来检查合成微生物联盟的行为是如何由细胞生长控制的种群动态和细胞间信号控制的内部转录动态之间的相互作用产生的。具体地说，我们研究了一个合成的微生物联合体，在该联合体中，两个菌株各自产生下调对方转录的信号。在单个菌株中，这种调控拓扑被称为“共抑制拨动开关”，可以导致双稳。我们发现，在一个由两个菌株组成的合成微生物联盟中，不同状态的存在和稳定性取决于相互作用的菌株在种群水平上的动态。当这两个菌株被动地争夺菌落内的空间时，它们的相对比例可能会波动，从而改变细胞间信号的强度。这些波动可能会推动财团走向替代均衡。此外，如果菌株的生长速度取决于它们的转录状态，就会产生一个额外的反馈环，从而产生松弛振荡。这些发现表明，微生物联合体的动态不能仅从它们的调控拓扑结构中预测，而且还由菌株之间的相互作用决定。
Synthetic microbial consortia are conglomerations of multiple strains of genetically engineered microbes programmed to cooperatively bring about population-level phenotypes. By coordinating their activity, the constituent strains can display emergent behaviors that are difficult to engineer into isogenic populations. To do so, strains are engineered to communicate with one another through intercellular signaling pathways. As a result, the regulatory networks that control gene transcription throughout the population are sensitive to the extracellular concentration of the signaling molecules, and hence the relative densities of constituent strains. Here, we use computational modeling to examine how the behavior of a synthetic microbial consortium results from the interplay between the population dynamics governed by cell growth and the internal transcriptional dynamics governed by cell-to-cell signaling. Specifically, we examine a synthetic microbial consortium in which two strains each produce signals that down-regulate transcription in the other. Within a single strain this regulatory topology is called a “co-repressive toggle switch” and can lead to bistability. We find that in a two-strain synthetic microbial consortium the existence and stability of different states depends on the population-level dynamics of the interacting strains. As the two strains passively compete for space within the colony, their relative fractions can fluctuate and thus alter the strengths of intercellular signals. These fluctuations can drive the consortium to alternative equilibria. Additionally, if the growth rates of the strains depend on their transcriptional states, an additional feedback loop is created that can generate relaxation oscillations. These findings demonstrate that the dynamics of microbial consortia cannot be predicted from their regulatory topologies alone, but also is determined by interactions between the strains.
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影响因子：
2
作者：
Veliz-Cuba A;Gupta C;Bennett MR;Josić K;Ott W
通讯作者：
Ott W
影响因子：
64.5
作者：
Tabor JJ;Salis HM;Simpson ZB;Chevalier AA;Levskaya A;Marcotte EM;Voigt CA;Ellington AD
通讯作者：
Ellington AD
影响因子：
64.8
作者：
Regot, Sergi;Macia, Javier;Sole, Ricard
通讯作者：
Sole, Ricard
影响因子：
56.9
作者：
Xie, Zhen;Wroblewska, Liliana;Benenson, Yaakov
通讯作者：
Benenson, Yaakov
DOI：
10.1126/science.aaa3794
发表时间：
2015-08-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen Y;Kim JK;Hirning AJ;Josić K;Bennett MR
通讯作者：
Bennett MR