Designer cells programming quorum-sensing interference with microbes
| Autor: | Ferdinand Sedlmayer, David Ausländer, Marius Müller, Martin Fussenegger, Dennis Hell |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell signaling Science 030106 microbiology General Physics and Astronomy Human pathogen Biosensing Techniques General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences Synthetic biology Lactones Bacterial Proteins Candida albicans Homoserine Animals Humans lcsh:Science Cell Engineering Vibrio Multidisciplinary biology Chemistry Biofilm Quorum Sensing Reproducibility of Results Chemotaxis Drug Resistance Microbial General Chemistry biochemical phenomena metabolism and nutrition biology.organism_classification Receptors Formyl Peptide 3. Good health Cell biology Quorum sensing 030104 developmental biology Genes Bacterial Biofilms lcsh:Q Synthetic Biology Signal transduction Bacteria Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Nature Communications, 9 |
| ISSN: | 2041-1723 |
| Popis: | 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. Bacterial populations communicate with AI-2 signaling molecules, helping to coordinate biofilm development and other group behaviors. Here the authors design a genetic circuit for mammalian cells that allows them to sense bacterial populations and interfere with quorum communication. |
| Databáze: | OpenAIRE |
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