The engineered strain worked fine in laboratory experiments, but gradually disappeared when the team introduced it into the gut of the mouse itself. It turned out that it had been outcompeted by the animal's native gut bacteria. The team did not fret in the face of this result because they knew that the classical strain of E. coli they used had lived only in the laboratory since the 1940s losing its ability to compete in the real world, particularly in an environment as challenging as the mammalian gut.
They tackled the problem by isolating a native strain of E. coli from the mouse gut, then engineering its genome to incorporate the switch. The switch in the cells flipped within hours, as it had before, and the cells "remembered" for about a week that they had seen the antibiotic in the gut, Kotula said. Moreover, the population stabilized within the gut, holding its own in the presence of other bacteria.
The team envisions a day when a doctor would give a patient a strain of engineered bacteria as a diagnostic, much as they give a probiotic today. The strain would be rigged to monitor the gut for any number of conditions from inflammation to disease markers. At a follow-up visit, the patient would submit a stool sample, and medical technicians would collect E. coli from the sample and analyze it. Only if the switch (or switches) were on would the doctor perform more invasive tests such as an endoscopy or a colonoscopy.
For now the team is focusing on genetically tweaking the memory element of their system so that the cells remember for even longer periods of time, and engineering it so the switch flips when it senses other chemical signatures as well, such as those of cancer or parasites. In the longer term, their engineered bacteria could sense a disease st
|Contact: Kristen Kusek|
Wyss Institute for Biologically Inspired Engineering at Harvard