Mining the gut microbiota, the trillions of microbes living in our digestive system is a promising approach for developing new sensors providing a response to disease and abnormalities in the body. To date, these efforts have largely relied on fecal samples, however, to obtain an instantaneous snapshot of bacterial behavior inside the gut using these techniques, invasive sampling is required via colonoscopy or a biopsy. Now, a study from researchers at Harvard University engineers synthetic bacterial memory circuits enabling microbial diagnostics for sensing biomolecules in the gut. The team states they have developed an effective, non-invasive way to quickly identify new bacterial biosensors which can recognize and report the presence of various disease triggers in the gut, helping set the stage for a new frontier of digestive health monitoring and treatment. The opensource study is published in the journal mSystems.

Recent studies from the lab designed a genetic circuit consisting of a memory element derived from a virus and a synthetic trigger element capable of detecting and recording the presence of a deactivated version of the antibiotic tetracycline. The synthetic circuit was integrated into the genomes of E. coli bacteria introduced into live mice consequently fed tetracycline. This caused the trigger in the bacterial circuit to activate the memory element that remained on for a week, however, this was just one molecule with real-world diagnostics rapidly testing multiple disease signals. The current study updates the past circuit to sense a variety of molecular signals.

The current study develops a library of different strains of E. coli, each containing synthetic memory circuitry and a unique trigger element in its genome; this library of bacterial strains was introduced into the guts of live mice. Results show the memory elements were turned on during passage through the mice. Data findings show two of the strains, in particular, showed consistent activation, even when given to mice in isolation, indicating they were activated by conditions inside the mice’s gut and could serve as sensors of gut-specific signals.

The experiment was repeated using a smaller library of E. coli strains whose trigger elements were genetic sequences thought to be associated with inflammation, ten of which were activated during transit through the mice. The team state they have engineered a memory circuit for parallel, high-throughput screening of hundreds of potential triggers, and apply this method to identify new triggers responding specifically to the gut environment. They go on to add through comparison between healthy mice and those suffering from inflammation, triggers responding differently during disease were also identified. They conclude these results provide a platform for in vivo noninvasive biosensor trigger discovery and longitudinal testing.

The team surmises they have engineered a synthetic bacterial memory as a biosensor trigger screening tool for gut microbiota. For the future, the researchers state their study is a step closer to engineering complex signaling pathways in bacteria which allow them to detect and even treat diseases long-term.

Source: Wyss Institute at Harvard University

 

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