Designer cells programming quorum-sensing interference with microbes

Ferdinand Sedlmayer, Dennis Hell, Marius Müller, David Ausländer and Martin Fussenegger ()
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Ferdinand Sedlmayer: ETH Zürich
Dennis Hell: ETH Zürich
Marius Müller: ETH Zürich
David Ausländer: ETH Zürich
Martin Fussenegger: ETH Zürich

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04223-7

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