Programmable bacteria detect and record an environmental signal in the mammalian gut

Abstract

Significance The human microbiota represents the trillions of bacteria that live on the skin, in the oral, nasal, and aural cavities, and throughout the gastrointestinal tract. The species that live in the gastrointestinal tract, the gut microbiota, closely interact with host cells and have a profound impact on health. To develop tools to effectively monitor the gut microbiota and ultimately help in disease diagnosis, we have engineered Escherichia coli to sense and record environmental stimuli, and demonstrated that E. coli with such memory systems can survive and function in the mammalian gut. This work demonstrates that E. coli can be engineered into living diagnostics capable of nondestructively probing the mammalian gut.

Synthetic biology devices for in vitro and in vivo diagnostics

“…To this end, E. coli were programmed to serve as "living diagnostics" and report environmental signals in the mouse gut (Fig. 2E) (50). This concept was accomplished by implanting the bacteria with a memory element based on the phage lambda cI/cro genetic switch (51).…”

A Synthetic Mammalian Therapeutic Gene Circuit for Sensing and Suppressing Inflammation

“…51 Detection of in vivo anti-inflammatory device activation ( Figures 4E and 4F), representing an inflammatory episode, could serve as a diagnostic reporter of an ongoing inflammatory process or as a log of past inflammatory events, without having to frequently sample the body fluids of an organism.…”

Rapid genome recoding by iterative recombineering of synthetic DNA

“…This strain contains the largest number of codon substitutions in a single recoded organism published to date. A recoded designer S. typhimurium could have diagnostic and therapeutic applications in the human body [11][12][13] . To demonstrate the power of our recoding approach, we replaced leucine codons due to their high frequency and redundancy in the Salmonella genome 14 .…”