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Scientific Method / Science & Exploration

Bacteria with “memory construct” snoops on our colon

Records the presence of small molecules while passing through the digestive tract.

Sue

If only it were easier to monitor and record what happens in our guts, the source of those feelings we can't explain but know instinctively are right. A wide variety of health conditions, from infections to cancer, take place out of sight in our abdomen. Sure, you could have a capsule endoscopy—swallow a camera-in-a-pill that takes photos of your intestines and sends them to a recorder you wear around your waist—but cameras have limitations. They can only record visuals of what's there, and they can't respond to changes, like the addition of a drug or a toxin.

Now, researchers at Harvard have engineered bacteria that can sense an environmental signal in a mouse gut and then report back about it. They hope that these bacteria will provide a nondestructive way to diagnose, and maybe even treat, intestinal maladies.

Synthetic biologists have generated a number of genetic "memory switches." The one used here relies on the different phases in the lifestyle of a virus that attacks the bacteria, called bacteriophage lambda. The virus has two distinct approaches: lysogenic phase, in which it just lurks in the bacterial cell, co-opting its DNA replication machinery; and the lytic phase, in which the phage destroys the bacterial cell it is infecting.

The genes controlling these two phases act as a stable switch. They repress each other, but each gene stimulates its own expression. Thus the one state will dominate until a stimulus induces the other—and once that is established, it is maintained stably as well.

By putting such a switch into E. coli, the scientists made bacteria that can switch from one stable state to another upon exposure to a specific stimulus; in this case, exposure to the antibiotic tetracycline. Once exposed, it takes the cells four cell divisions—a couple of hours—to switch states, and once they do they remain in their memory state for days.

This held true not only in petri dishes, but also in mouse guts; and it held true not only for a lab strain of E. coli engineered to contain the memory switch, but it also worked when the researchers inserted the memory switch into an uncharacterized strain of E. coli isolated from mouse guts.

Unlike a camera, these bacteria can't monitor all that they see; they can only test for the presence of an environmental agent, one that must be known beforehand. But it would be possible to make switches based on a variety of other environmental signals. Inflammation, cancer, parasites, and assorted environmental toxins all leave recognizable chemical signatures in the gut. Engineered bacteria may one day serve to diagnose a specific pathogen, and maybe one day to administer the appropriate therapeutic, in a nondestructive way.

PNAS, 2014. DOI: 10.1073/pnas.1321321111  (About DOIs).

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