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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 signal...

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Autores principales: Scott, Spencer R., Din, M Omar, Bittihn, Philip, Xiong, Liyang, Tsimring, Lev S., Hasty, Jeff
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603288/
https://www.ncbi.nlm.nih.gov/pubmed/28604679
http://dx.doi.org/10.1038/nmicrobiol.2017.83
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author Scott, Spencer R.
Din, M Omar
Bittihn, Philip
Xiong, Liyang
Tsimring, Lev S.
Hasty, Jeff
author_facet Scott, Spencer R.
Din, M Omar
Bittihn, Philip
Xiong, Liyang
Tsimring, Lev S.
Hasty, Jeff
author_sort Scott, Spencer R.
collection PubMed
description 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.
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spelling pubmed-56032882017-12-12 A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis Scott, Spencer R. Din, M Omar Bittihn, Philip Xiong, Liyang Tsimring, Lev S. Hasty, Jeff Nat Microbiol Article 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. 2017-06-12 /pmc/articles/PMC5603288/ /pubmed/28604679 http://dx.doi.org/10.1038/nmicrobiol.2017.83 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Scott, Spencer R.
Din, M Omar
Bittihn, Philip
Xiong, Liyang
Tsimring, Lev S.
Hasty, Jeff
A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis
title A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis
title_full A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis
title_fullStr A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis
title_full_unstemmed A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis
title_short A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis
title_sort stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603288/
https://www.ncbi.nlm.nih.gov/pubmed/28604679
http://dx.doi.org/10.1038/nmicrobiol.2017.83
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