Bacteria can be engineered to function as diagnostics or therapeutics in the mammalian gut but commercial translation of technologies to accomplish this has been hindered by the susceptibility of synthetic genetic circuits to mutation and unpredictable function during extended gut colonization. Here, we report stable, engineered bacterial strains that maintain their function for 6 months in the mouse gut. We engineered a commensal murine Escherichia coli strain to detect tetrathionate, which is produced during inflammation. Using our engineered diagnostic strain, which retains memory of exposure in the gut for analysis by fecal testing, we detected tetrathionate in both infection-induced and genetic mouse models of inflammation over 6 months. The synthetic genetic circuits in the engineered strain were genetically stable and functioned as intended overtime. The durable performance of these strains confirms the potential of engineered bacteria as living diagnostics.

My takeaways:

1. We are all aware of the growing impact that having and maintaining a healthy gut microbiome can have a person’s overall health. The results presented here are exciting because of the potential to engineer bacteria to both non-invasively track a disease, but also the potential to engineer bacteria to treat various diseases.

2. The exciting finding, while preliminary, is that these researcher found a way to get engineered bacterial to colonize in the gut and remain there for over 6 months. This is the major breakthrough in this paper.

Nature Biotechnology, 2017, Vol 35, p 653-658

Pamela Silver from the Department of Systems Biology in Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering at Harvard University

Her work is supported by the NIH