TY - JOUR T1 - Adaptive strategies of the candidate probiotic <em>E. coli</em> Nissle in the mammalian gut JF - bioRxiv DO - 10.1101/364505 SP - 364505 AU - Nathan Crook AU - Aura Ferreiro AU - Andrew J. Gasparrini AU - Mitchell Pesesky AU - Molly K. Gibson AU - Bin Wang AU - Xiaoqing Sun AU - Zevin Condiotte AU - Stephen Dobrowolski AU - Daniel Peterson AU - Gautam Dantas Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/07/09/364505.abstract N2 - 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. By exposing the candidate probiotic E. coli Nissle (EcN) to the mouse gastrointestinal tract over several weeks, we uncovered the consequences of gut transit, inter-species competition, antibiotic pressure, and engineered genetic function on the processes under selective pressure during both within-genome and horizontal evolutionary modes. We then show the utility of EcN as a chassis for engineered function by achieving the highest reported reduction in serum phenylalanine levels in a mouse model of phenylketonuria using an engineered probiotic. Collectively, we demonstrate a generalizable pipeline which can be applied to other probiotic strains to better understand their safety and engineering potential. ER -