Microbial ecologists are increasingly turning to small, synthesized ecosystems^1-5 as a reductionist tool to probe the complexity of native microbiomes^6,7. Concurrently, synthetic biologists have gone from single-cell gene circuits^8-11 to controlling whole populations using intercellular signalling^12-16. The intersection of these fields is giving rise to new approaches in waste recycling¹⁷, industrial fermentation¹⁸, bioremediation¹⁹ and human health^16,20. These applications share a common challenge⁷ well-known in classical ecology^21,22-stability of an ecosystem cannot arise without mechanisms that prohibit the faster-growing species from eliminating the slower. Here, we combine orthogonal quorum-sensing systems and a population control circuit with diverse self-limiting growth dynamics to engineer two 'ortholysis' circuits capable of maintaining a stable co-culture of metabolically competitive Salmonella typhimurium strains in microfluidic devices. Although no successful co-cultures are observed in a two-strain ecology without synthetic population control, the 'ortholysis' design dramatically increases the co-culture rate from 0% to approximately 80%. Agent-based and deterministic modelling reveal that our system can be adjusted to yield different dynamics, including phase-shifted, antiphase or synchronized oscillations, as well as stable steady-state population densities. The 'ortholysis' approach establishes a paradigm for constructing synthetic ecologies by developing stable communities of competitive microorganisms without the need for engineered co-dependency.

中文翻译：

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使用合成群体调节裂解来稳定自限性细菌的微生物生态系统。


微生物生态学家越来越多地转向小型综合生态系统^1-5作为探索天然微生物组复杂性的简化工具^6,7 。与此同时，合成生物学家已经从单细胞基因回路^8-11转向使用细胞间信号传导控制整个群体^12-16 。这些领域的交叉正在催生废物回收¹⁷ 、工业发酵¹⁸ 、生物修复¹⁹和人类健康^{16,20 方面}的新方法。这些应用面临着经典生态学中众所周知的共同挑战^{7 21,22 -}如果没有阻止生长较快的物种消灭生长较慢的物种的机制，生态系统的稳定性就不可能出现。在这里，我们将正交群体感应系统和具有多种自限生长动力学的群体控制电路结合起来，设计了两个“正解”电路，能够在微流体装置中维持代谢竞争性鼠伤寒沙门氏菌菌株的稳定共培养。尽管在没有综合群体控制的情况下，在两种菌株生态中没有观察到成功的共培养，但“正向分解”设计将共培养率从 0% 显着提高到大约 80%。基于代理的确定性建模表明，我们的系统可以进行调整以产生不同的动态，包括相移、反相或同步振荡，以及稳定的稳态人口密度。 “正解”方法通过开发稳定的竞争性微生物群落而无需工程化的相互依赖性，建立了构建合成生态学的范例。