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Designer cells programming quorum-sensing interference with microbes

Author

Listed:
  • Ferdinand Sedlmayer

    (ETH Zürich)

  • Dennis Hell

    (ETH Zürich)

  • Marius Müller

    (ETH Zürich)

  • David Ausländer

    (ETH Zürich)

  • Martin Fussenegger

    (ETH Zürich
    University of Basel)

Abstract

Quorum sensing is a promising target for next-generation anti-infectives designed to address evolving bacterial drug resistance. The autoinducer-2 (AI-2) is a key quorum-sensing signal molecule which regulates bacterial group behaviors and is recognized by many Gram-negative and Gram-positive bacteria. Here we report a synthetic mammalian cell-based microbial-control device that detects microbial chemotactic formyl peptides through a formyl peptide sensor (FPS) and responds by releasing AI-2. The microbial-control device was designed by rewiring an artificial receptor-based signaling cascade to a modular biosynthetic AI-2 production platform. Mammalian cells equipped with the microbial-control gene circuit detect formyl peptides secreted from various microbes with high sensitivity and respond with robust AI-2 production, resulting in control of quorum sensing-related behavior of pathogenic Vibrio harveyi and attenuation of biofilm formation by the human pathogen Candida albicans. The ability to manipulate mixed microbial populations through fine-tuning of AI-2 levels may provide opportunities for future anti-infective strategies.

Suggested Citation

  • Ferdinand Sedlmayer & Dennis Hell & Marius Müller & David Ausländer & Martin Fussenegger, 2018. "Designer cells programming quorum-sensing interference with microbes," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04223-7
    DOI: 10.1038/s41467-018-04223-7
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    Cited by:

    1. Shengbo Wu & Jie Feng & Chunjiang Liu & Hao Wu & Zekai Qiu & Jianjun Ge & Shuyang Sun & Xia Hong & Yukun Li & Xiaona Wang & Aidong Yang & Fei Guo & Jianjun Qiao, 2022. "Machine learning aided construction of the quorum sensing communication network for human gut microbiota," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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