The human gut comprises an intricate ecosystem of trillions of bacteria that continuously sense and respond to signals from their environment. Some of these signals could provide valuable information for the detection of gastrointestinal conditions such as Crohn's disease that have been difficult to diagnose early and accurately.

Now scientists have found a way to harness these bacterial responses to the goings-on in the gut, using synthetic biology. In a collaboration between Harvard University's Wyss Institute for Biologically Inspired Engineering and Harvard Medical School, both in Boston, MA, a newly engineered strain of Escherichia coli bacteria was developed that can record a specific biological event in the gut and report back the information later, almost like a memory.

The team, led by Pamela Silver, genetically inserted a transcriptional switch into the E. coli that 'flips' when it senses a specific environmental cue. This switch came from lambda phage, a virus that commonly attaches to the bacterium. After invading E. coli, lambda lies dormant, its DNA biding its time in the E. coli's genome. But when the bacterium's DNA is damaged, such as after exposure to an antibiotic, the genomic switch flips, changing the expression of particular proteins in the bacterial cell. Later, one can check whether the switch has been flipped in the E. coli by checking the cell's protein levels.

Jeff Way, coauthor of the paper, said, “Nature has a tried and true blueprint for memory systems if you know where to look.” Added lead author Jonathan Kotula, “We knew the lambda switch would be a great candidate for the memory element, and we simply tweaked it to meet our needs.”

The researchers tested their switch in a strain of E. coli isolated from the mouse's gut so that it would be robust enough to compete with the animal's native bacteria. After engineering its genome to incorporate the switch, they administered the bacteria back to the mouse, which had also been given the chemical anhydrotetracycline. Within a few hours, the bacteria sensed the chemical and flipped the genetic switch, which then stayed flipped for about a week (Proc. Natl. Acad. Sci. USA doi:10.1073/pnas.1321321111; published online 17 March 2014). This was long enough for scientists to recover fecal samples from the mouse and test them in order to determine whether the chemical signal had been detected and recorded. “This achievement paves the way toward living monitors programmed using synthetic gene circuits,” said Silver.