Adaptive strategies of the candidate probiotic E. coli Nissle in the mammalian gut
| Autor: | Andrew J. Gasparrini, Xiaoqing Sun, Stephen Dobrowolski, Aura Ferreiro, Nathan Crook, Zevin Condiotte, Mitchell W. Pesesky, Molly K. Gibson, Bin Wang, Daniel A. Peterson, Gautam Dantas |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Engineered genetic
Phenylalanine Adaptation Biological Computational biology Biology Microbiology Genome Article law.invention Fight-or-flight response 03 medical and health sciences Mice Probiotic 0302 clinical medicine Gastrointestinal Agents law Virology Phenylketonurias Escherichia coli Animals Humans Microbiome Selection Genetic 030304 developmental biology 0303 health sciences Competitive fitness Strain (biology) Probiotics Microbiota Brain Gastrointestinal Tract Disease Models Animal Metabolism Mutation Mouse Gastrointestinal Tract Parasitology 030217 neurology & neurosurgery Function (biology) |
| Popis: | Summary Probiotics are living microorganisms that are increasingly used as gastrointestinal therapeutics by virtue of their innate or engineered genetic function. Unlike abiotic therapeutics, probiotics can replicate in their intended site, subjecting their genomes and therapeutic properties to natural selection. We exposed the candidate probiotic E. coli Nissle (EcN) to the mouse gastrointestinal tract over several weeks, systematically altering the diet and background microbiota complexity. In-transit EcN accumulates genetic mutations that modulate carbohydrate utilization, stress response, and adhesion to gain competitive fitness, while previous exposure to antibiotics reveals an acquisition of resistance. We then leveraged these insights to generate an EcN strain that shows therapeutic efficacy in a mouse model of phenylketonuria and found that it was genetically stable over 1 week, thereby validating EcN’s utility as a chassis for engineering. Collectively, we demonstrate a generalizable pipeline that can be applied to other probiotics to better understand their safety and engineering potential. |
| Databáze: | OpenAIRE |
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