E. coli strain Nissle 1917 (EcN) is widely taken orally as a probiotic and is also amenable to standard genetic engineering techniques, so it is a potentially attractive chassis for bacterial therapeutics. However, the low pH in the stomach and high bile salt concentration in the bile ducts and gallbladder dramatically reduce EcN cell viability, thus hindering therapeutic applications in the intestine. To improve tolerance to acid and bile salt, we performed continuous adaptive evolution on EcN and recovered mutated strains with greater tolerance to low pH or high bile salt. Unexpectedly, evolved EcN also exhibited greater adhesivity to an intestinal cell line in vitro, which may be an additional beneficial property in therapeutic applications. We will also discuss the mutational basis for pH and bile tolerance and their implications for biomedical applications such as oral delivery of therapeutic bacteria.

Continuous evolution of Escherichia coli Nissle 1917 for biomedical applications

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.