Coupling spatial segregation with synthetic circuits to control bacterial survival.

Coupling spatial segregation with synthetic circuits to control bacterial survival.
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DOI:
10.15252/msb.20156567
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发表时间:
2016-02-29
影响因子:
9.9
通讯作者:
You L
You L
中科院分区:
生物学1区
文献类型:
--
作者:
Huang S;Lee AJ;Tsoi R;Wu F;Zhang Y;Leong KW;You L

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工程细菌在医学和环境应用方面具有巨大的潜力。实现这种潜力需要对工程行为的可控性和工程系统的可伸缩性。在这里,我们提出了一种平台技术——微生物群机器人,它利用空间排列来控制工程细菌的生长动态。作为原理的证明,我们展示了一种保护策略来防止意外的细菌增殖。特别是,我们采用了几个合成基因电路来编程大肠杆菌的集体生存:工程细菌只有在足够高的种群密度下才能存活。当被可渗透膜包裹时,这些细菌可以感知当地环境并做出相应的反应。微生物群机器人胶囊内的细胞因其高密度而存活。然而,那些从胶囊中逃脱的人会因为密度下降而被杀死。我们证明了这种设计概念是模块化的,并且易于推广。我们的工作为多种应用的混合生物材料系统的工程集成和可编程控制奠定了基础。
Engineered bacteria have great potential for medical and environmental applications. Fulfilling this potential requires controllability over engineered behaviors and scalability of the engineered systems. Here, we present a platform technology, microbial swarmbot, which employs spatial arrangement to control the growth dynamics of engineered bacteria. As a proof of principle, we demonstrated a safeguard strategy to prevent unintended bacterial proliferation. In particular, we adopted several synthetic gene circuits to program collective survival in Escherichia coli: the engineered bacteria could only survive when present at sufficiently high population densities. When encapsulated by permeable membranes, these bacteria can sense the local environment and respond accordingly. The cells inside the microbial swarmbot capsules will survive due to their high densities. Those escaping from a capsule, however, will be killed due to a decrease in their densities. We demonstrate that this design concept is modular and readily generalizable. Our work lays the foundation for engineering integrated and programmable control of hybrid biological–material systems for diverse applications.