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

Nat Microbiol. 2017 Jun 12;2:17083. doi: 10.1038/nmicrobiol.2017.83.

Abstract

Microbial ecologists are increasingly turning to small, synthesized ecosystems1-5 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.

MeSH terms

  • Bacteria / growth & development*
  • Bacteria / metabolism
  • Bacteriolysis
  • Coculture Techniques
  • Ecosystem*
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism
  • Humans
  • Lab-On-A-Chip Devices
  • Microbial Interactions* / genetics
  • Models, Biological
  • Quorum Sensing*
  • Rhodopseudomonas / genetics
  • Rhodopseudomonas / metabolism
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / metabolism
  • Synthetic Biology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Transcription Factors