A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis

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 signaling(12–16). The intersection of these fields is giving rise to new approaches in waste recycling,(17) industrial fermentation(18), bioremediation(19), and human health(16,20). These applications share a common challenge(7) 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 in order to engineer two ‘ortholysis’ circuits capable of maintaining a stable co-culture of metabolically competitive strains in microfluidic devices. While 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 modeling reveal that our system can be adjusted to yield different dynamics, including phase-shifted, anti-phase 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 microbes without the need for engineered codependency.