Embedded Files
Inducible cell-to-cell signaling for tunable dynamics in microbial communities
Miano, A., Liao, M.J. & Hasty, J. Nature Communications 11, 1193 (2020). https://doi.org/10.1038/s41467-020-15056-8
Synthetic biology has the potential to revolutionize both healthcare and industry, with applications ranging from therapeutics1,2,3,4 and drug delivery5,6,7, to bioproduction8 and bioremediation9. These emerging applications have uncovered the need to engineer spatially extended complex multi-cellular populations, requiring new tools that can bridge the gap between single cell, population, and community level engineering10,11,12,13. To achieve this, significant research efforts have been focused on engineering and characterizing a variety of cell-to-cell communication systems, with a particular focus on bacterial quorum sensing14,15,16,17. Currently, the majority of quorum sensing systems used in synthetic biology rely on self-produced small molecules that result in spatially and temporally self-organized systems, which can not be easily externally regulated15,18,19,20,21. In this study, we propose a tool that combines two pillars of population control: inducibility and cell-to-cell communication. To design this inducible quorum sensing system (iQS), we took inspiration from the native components of the photosynthetic bacterium Rhodopseudomonas palustris, which relies on a plant derived organic compound for the production of its signaling molecule22. This inducer, p-coumaric acid (pCA), is a ubiquitous molecule present in most fruits and vegetables23 and has proven to be safe for both bacteria24,25 and human cells26,27 at relevant concentrations.
41467_2020_15056_MOESM7_ESM (1).mp441467_2020_15056_MOESM6_ESM (1).mp4Survival of the weakest in non-transitive asymmetric interactions among strains of E. coli.
Liao, M.J*., Miano, A*., Nguyen, C.B. et al. Nature Communications 11, 6055 (2020). https://doi.org/10.1038/s41467-020-19963-8
Hierarchical organization in ecology, whereby interactions are nested in a manner that leads to a dominant species, naturally result in the exclusion of all but the dominant competitor. Alternatively, non-hierarchical competitive dynamics, such as cyclical interactions, can sustain biodiversity. Here, we designed a simple microbial community with three strains of E. coli that cyclically interact through (i) the inhibition of protein production, (ii) the digestion of genomic DNA, and (iii) the disruption of the cell membrane. We find that intrinsic differences in these three major mechanisms of bacterial warfare lead to an unbalanced community that is dominated by the weakest strain. We also use a computational model to describe how the relative toxin strengths, initial fractional occupancies, and spatial patterns affect the maintenance of biodiversity. The engineering of active warfare between microbial species establishes a framework for exploration of the underlying principles that drive complex ecological interactions.
41467_2020_19963_MOESM11_ESM.mp441467_2020_19963_MOESM13_ESM (1).mp441467_2020_19963_MOESM9_ESM.mp4Page updated
Google Sites
Report abuse