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Transcriptional programming in a Bacteroides consortium

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Listed:
  • 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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    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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