Applying the design-build-test paradigm in microbiome engineering

Pham, Hoang Long; Ho, Chun Loong; Wong, Adison; Lee, Yung Seng; Chang, Matthew Wook

doi:10.1016/j.copbio.2017.03.021

Cited by 15 publications

(9 citation statements)

References 69 publications

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“…This activity also provides the opportunity to teach students the concept of the design-build-test cycle, a common paradigm used by synthetic biologists when developing new genetic circuits ( 28 ). Once students choose the visual output they would like to engineer, they can design an experiment to mix fluorescent proteins in different ratios to achieve their goal.…”

Section: Resultsmentioning

confidence: 99%

BioBits™ Explorer: A modular synthetic biology education kit

et al. 2018

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Section: Resultsmentioning

confidence: 99%

BioBits™ Explorer: A modular synthetic biology education kit

et al. 2018

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“…Another prominent example of the “add” approach is bioaugmentation, one of the methods of bioremediation, in which cultured microorganisms are inoculated into the natural microbiota to help remove contaminants [108]. Similarly, the administration of probiotics to animals and plants is also an example of the “add” approach [109, 110]. Most of these past studies showed that the effects of the addition of microbes did not last for long and the exogenous microbes were kicked out over time ( e.g., 3-chloroaniline degrading bacterium into activated sludge [111]).…”

Section: Enriched Model Systemsmentioning

confidence: 99%

Model Microbial Consortia as Tools for Understanding Complex Microbial Communities

Haruta

Yamamoto

2018

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A major biological challenge in the postgenomic era has been untangling the composition and functions of microbes that inhabit complex communities or microbiomes. Multi-omics and modern bioinformatics have provided the tools to assay molecules across different cellular and community scales; however, mechanistic knowledge over microbial interactions often remains elusive. This is due to the immense diversity and the essentially undiminished volume of not-yet-cultured microbes. Simplified model communities hold some promise in enabling researchers to manage complexity so that they can mechanistically understand the emergent properties of microbial community interactions. In this review, we surveyed several approaches that have effectively used tractable model consortia to elucidate the complex behavior of microbial communities. We go further to provide some perspectives on the limitations and new opportunities with these approaches and highlight where these efforts are likely to lead as advances are made in molecular ecology and systems biology.

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“…Whether such encounters are transient or will lead to long-term colonization, is influenced by complex ecological interactions between the invading species and the existing consortium, as well as the host’s dietary habits and the physiology of the intestine (David et al, 2014; Wotzka et al, 2019). A better understanding of the factors determining colonization efficiency is crucial in the development of microbiota engineering strategies (Donia, 2015; Pham et al, 2017; Sheth et al, 2016) and in the use of bacterial species as biosensors to probe microbiota function and stability (Goodman et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Fitness advantage of Bacteroides thetaiotaomicron capsular polysaccharide is dependent on the resident microbiota

Hoces

Greter

Arnoldini

et al. 2022

Preprint

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Many microbiota-based therapeutics rely on our ability to introduce a microbe of choice into an already-colonized intestine. However, we remain largely blind to the quantitative effects of processes determining colonization success. In this study, we used genetically-barcoded Bacteroides thetaiotaomicron (B.theta) strains in combination with mathematical modeling to quantify population bottlenecks experienced by B.theta during gut colonization. Integrating population bottlenecks sizes with careful quantification of net growth rates in vitro and in vivo allows us to build models describing the events during intestinal colonization in the context of gnotobiotic and complex microbiotas. Using these models, we estimated the decrease in niche size for B.theta colonization with increasing microbiota complexity. In addition, our system can be applied to mechanistically dissect colonization defects of mutant strains. As a proof of concept, we demonstrated that the competitive disadvantage of a B.theta mutant lacking capsular polysaccharide is due to a combination of an increased lag-phase before growth initiation in the gut, combined with an increased clearance rate. Crucially, the requirement for the B.theta capsule depended strongly on microbiota composition, suggesting that the dominant role may be protection from bacterial or phage aggression rather than from host-induced bactericidal mechanisms.

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Applying the design-build-test paradigm in microbiome engineering

Cited by 15 publications

References 69 publications

BioBits™ Explorer: A modular synthetic biology education kit

BioBits™ Explorer: A modular synthetic biology education kit

Model Microbial Consortia as Tools for Understanding Complex Microbial Communities

Fitness advantage of Bacteroides thetaiotaomicron capsular polysaccharide is dependent on the resident microbiota

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