Trends in Biotechnology
ReviewEngineering microbial consortia: a new frontier in synthetic biology
Section snippets
Benefits and features of microbial consortia
Synthetic biology 1, 2, 3, 4, 5 has generated many examples of what microbes can do and what we can learn from them 6, 7, 8, 9, 10, 11 when they are creatively engineered in the laboratory environment. From the synthesis of an anti-malarial drug [12] to the study of microbial genetic competency [13], engineered microbes have advanced technology while providing insight into the workings of the cell. Interest has recently emerged in engineering microbial consortia – multiple interacting microbial
Mixed populations can perform complex tasks
Mixed populations can perform functions that are difficult or even impossible for individual strains or species. Balancing two or more tasks so that they are efficiently completed within one organism can pose insuperable challenges in some situations. For example, it is difficult to engineer efficient, metabolically independent pathways within a single cell to enable it to consume the five- and six-carbon sugars produced by lignocellulose degradation; asynchrony in degradation, caused by
Mixed populations can be robust to changes in environment
Living in community is thought both to generate robustness to environmental fluctuations and to promote stability through time for the members of a consortium. Compared with monocultures, communities might be more capable of resisting invasion by other species [19]. Furthermore, they might be able to weather periods of nutrient limitation better because of the diversity of metabolic modes available to a mix of species combined with the ability to share metabolites within the community [20]. For
Communication organizes function in engineered consortia
Communication among individuals or populations enables the division of labor that results in their ability to exhibit complex function. Communication in natural consortia can involve the exchange of dedicated signal molecules within or between single populations 14, 25. Bacteria coordinate intra-population behaviors from biofilm formation 26, 27, 28 to virulence 29, 30, 31 with the exchange of acyl-homoserine lactone (acyl-HSL) signaling molecules (in Gram-negative species) and small peptides
Synthetic consortia lend biological insight
Many questions remain regarding the evolution and stability of natural ecosystems. As Shou et al.[45] and Balagadde et al.[42] demonstrated, we can perturb microbial ecosystems by genetically engineering them to achieve different behaviors. Furthermore, we can control their growth environments. Given these abilities, we can explore the evolution of interacting species in ways that are impossible with larger organisms [46]. Such studies have already demonstrated that cheating strains,
Synthetic consortia in healthcare
Microbial consortia can carry out more complex functions, and they might be more robust to changes in their environments than are individual populations. These two traits make microbial consortia attractive as platforms for medical technology. Engineers have developed bacteria that serve as drug-delivery devices 49, 50, 51 and gene-delivery vehicles 50, 52, 53, but these technologies suffer a lack of precision in targeting and release. The greater complexity of function available, coupled with
Challenges in engineering microbial consortia
There are significant challenges associated with engineering microbial consortia, and these will require attention as engineers consider their potential applications. Although many of the challenges are shared with those faced when engineering single microbial populations, some are particular to controlling the behavior of multiple, interacting populations. First, natural microbial communities can maintain homeostasis; members generally do not out-compete one another and do not exhaust the
Conclusion
Because members of microbial consortia communicate and differentiate, consortia can perform more complex tasks and can survive in more changeable environments than can uniform populations. Simple engineered consortia might be described through mathematical models more easily than natural systems are, and they can be used to develop and validate models of more complex systems [60]. Furthermore, their behavior can be controlled by externally introduced signals (e.g. circuits can be induced by
Acknowledgements
Our research on synthetic microbial consortia is funded by the National Institutes of Health grant NIH 1-R01-CA118486. Thanks to Kevin Boulware and Michael Dougherty for helpful conversations.
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