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Transcriptional programming in a Bacteroides consortium

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  • Brian D. Huang

    (School of Chemical & Biomolecular Engineering)

  • Thomas M. Groseclose

    (School of Chemical & Biomolecular Engineering)

  • Corey J. Wilson

    (School of Chemical & Biomolecular Engineering)

Abstract

Bacteroides species are prominent members of the human gut microbiota. The prevalence and stability of Bacteroides in humans make them ideal candidates to engineer as programmable living therapeutics. Here we report a biotic decision-making technology in a community of Bacteroides (consortium transcriptional programming) with genetic circuit compression. Circuit compression requires systematic pairing of engineered transcription factors with cognate regulatable promoters. In turn, we demonstrate the compression workflow by designing, building, and testing all fundamental two-input logic gates dependent on the inputs isopropyl-β-D-1-thiogalactopyranoside and D-ribose. We then deploy complete sets of logical operations in five human donor Bacteroides, with which we demonstrate sequential gain-of-function control in co-culture. Finally, we couple transcriptional programs with CRISPR interference to achieve loss-of-function regulation of endogenous genes—demonstrating complex control over community composition in co-culture. This work provides a powerful toolkit to program gene expression in Bacteroides for the development of bespoke therapeutic bacteria.

Suggested Citation

  • Brian D. Huang & Thomas M. Groseclose & Corey J. Wilson, 2022. "Transcriptional programming in a Bacteroides consortium," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31614-8
    DOI: 10.1038/s41467-022-31614-8
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    References listed on IDEAS

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    1. Ronald E. Rondon & Thomas M. Groseclose & Andrew E. Short & Corey J. Wilson, 2019. "Transcriptional programming using engineered systems of transcription factors and genetic architectures," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
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    5. In Young Hwang & Elvin Koh & Adison Wong & John C. March & William E. Bentley & Yung Seng Lee & Matthew Wook Chang, 2017. "Engineered probiotic Escherichia coli can eliminate and prevent Pseudomonas aeruginosa gut infection in animal models," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    6. Johan Larsbrink & Theresa E. Rogers & Glyn R. Hemsworth & Lauren S. McKee & Alexandra S. Tauzin & Oliver Spadiut & Stefan Klinter & Nicholas A. Pudlo & Karthik Urs & Nicole M. Koropatkin & A. Louise C, 2014. "A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes," Nature, Nature, vol. 506(7489), pages 498-502, February.
    7. Thomas M. Groseclose & Ronald E. Rondon & Zachary D. Herde & Carlos A. Aldrete & Corey J. Wilson, 2020. "Engineered systems of inducible anti-repressors for the next generation of biological programming," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    8. Tanya Yatsunenko & Federico E. Rey & Mark J. Manary & Indi Trehan & Maria Gloria Dominguez-Bello & Monica Contreras & Magda Magris & Glida Hidalgo & Robert N. Baldassano & Andrey P. Anokhin & Andrew C, 2012. "Human gut microbiome viewed across age and geography," Nature, Nature, vol. 486(7402), pages 222-227, June.
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    Cited by:

    1. Brian D. Huang & Dowan Kim & Yongjoon Yu & Corey J. Wilson, 2024. "Engineering intelligent chassis cells via recombinase-based MEMORY circuits," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Andrew E. Short & Dowan Kim & Prasaad T. Milner & Corey J. Wilson, 2023. "Next generation synthetic memory via intercepting recombinase function," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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