A new strain of engineered bacteria can detect inflammation in the colon of mice even after more than 1,000 bacterial divisions, researchers report (Nat. Biotechnol. 2017, DOI: 10.1038/nbt.3879). Such a microbe could help doctors diagnose and monitor diseases such as inflammatory bowel disease.
Pamela A. Silver and coworkers at Harvard University engineered nonpathogenic Escherichia coli to detect and respond to tetrathionate, a transient product of a reactive oxygen species released by intestinal cells during inflammation.
The researchers inserted two genetic circuits into the bacterial genome. The first circuit produces the transcriptional factor Cro in response to tetrathionate, and Cro triggers a second “memory” circuit to produce the protein β-galactosidase. Even when tetrathionate is no longer around, the bacteria “remember” the exposure and continue to produce both proteins. The researchers monitored inflammation in mice treated with the microbes by measuring β-galactosidase in the animals’ feces.
The bacteria produced β-galactosidase in mice with intestinal infections and those genetically engineered to have high levels of inflammation. The researchers were even able to detect signs of inflammation in mice that had no visible signs of it, which suggests that the bacteria can detect low-level, subclinical inflammation.
Because the bacteria didn’t acquire mutations that shut down the engineered circuits, they could maintain their responsiveness to tetrathionate for at least six months, which equals approximately 1,600 generations of engineered bacteria.