1. A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis.
- Author
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Scott SR, Din MO, Bittihn P, Xiong L, Tsimring LS, and Hasty J
- Subjects
- Bacteria metabolism, Bacteriolysis, Coculture Techniques, Escherichia coli genetics, Escherichia coli growth & development, Escherichia coli metabolism, Humans, Lab-On-A-Chip Devices, Models, Biological, Rhodopseudomonas genetics, Rhodopseudomonas metabolism, Salmonella typhimurium growth & development, Salmonella typhimurium metabolism, Transcription Factors genetics, Transcription Factors metabolism, Bacteria growth & development, Ecosystem, Microbial Interactions genetics, Quorum Sensing, Synthetic Biology
- Abstract
Microbial ecologists are increasingly turning to small, synthesized ecosystems
1-5 as a reductionist tool to probe the complexity of native microbiomes6,7 . Concurrently, synthetic biologists have gone from single-cell gene circuits8-11 to controlling whole populations using intercellular signalling12-16 . The intersection of these fields is giving rise to new approaches in waste recycling17 , industrial fermentation18 , bioremediation19 and human health16,20 . These applications share a common challenge7 well-known in classical ecology21,22 -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.- Published
- 2017
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