[Nature Microbiology] A stabilized microbial ecosystem of self-limiting bacteria using synthetic quo
Microbial ecologists are increasingly turning to small, synthesized ecosystems1,2,3,4,5 as a reductionist tool to probe the complexity of native microbiomes6,7. Concurrently, synthetic biologists have gone from single-cell gene circuits8,9,10,11 to controlling whole populations using intercellular signalling12,13,14,15,16. 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.
Spencer R. Scott, M. Omar Din, Philip Bittihn, Liyang Xiong, Lev S. Tsimring & Jeff Hasty Nature Microbiology 2, Article number: 17083 (2017) doi:10.1038/nmicrobiol.2017.83