Scientists Engineer Bacteria to Detect Colon Cancer

Sometime in the perhaps not-so-distant future, you may be able to skip a colonoscopy and opt for a dose of engineered bacteria instead.

Researchers successfully modified bacteria to detect specific tumor DNA sequences in the colons of mice, according to a study published Thursday in the journal Science. While it will be some time before such a system is ready for humans, the study represents the first time engineered bacteria have detected specific DNA sequences, a capability that could eventually be used to detect a range of cancers, infections and other diseases.

“I was kind of surprised by the paper,” said Timothy Lu, a synthetic biologist at the Massachusetts Institute of Technology, who wasn’t involved in the study. “The idea that engineered bacteria can pick up tumor-related DNA and detect it sensitively enough is actually pretty cool.”

Colonoscopy is currently the gold standard for detecting colorectal cancer, but can be very off-putting to patients. "There are people who don't want to do a colonoscopy, —it’s expensive, it’s uncomfortable," said Robert Cooper, a synthetic biologist at the University of California San Diego. "This could be much more patient friendly, like taking a probiotic pill.”

Bacteria have been tweaked to detect diseases before, including to sense signs of cancer and diabetes in urine. But no one had figured out how to get bacteria to sense specific sequences of DNA within an organism, a capability that could make it a lot easier to detect tumors early. 

Enter Acinetobacter baylyi, a well-studied bacteria that’s especially adept at stealing DNA from the environment. 

Many bacteria integrate genetic material from their surroundings, a capability called “natural competence” that allows the asexual microbes to mix up their genomes. If A. baylyi could be tweaked to look out for specific DNA sequences, like mutations commonly associated with colon tumors, it might be useful as an organic cancer detector.

The team engineered A. baylyi to find and steal a specific DNA sequence commonly associated with colon cancer in a gene called KRAS. Additionally, they built in a system that caused the engineered bacteria to turn on an antibiotic resistance gene whenever it detected tumor DNA. To see if the engineered bacteria detected cancer, all the researchers had to do was “spread samples on an antibiotic [petri dish] and count how many cells grow,” said Cooper. “It’s a standard procedure.”

Using antibiotic resistance to flag the presence of tumor DNA wouldn’t be a good idea in humans. "In the future, it'll be really interesting to see if they can couple detection to an output signal that's more rapidly detectable," said Lu. In principle, the signal could be anything bacteria can make.

The DNA-detection system worked remarkably well on mice who were given engineered tumors by the scientists. “Basically we got 100 percent discrimination between mice that had a tumor versus not,” said Cooper. It didn’t work as well on non-engineered mice. “Detection of non-engineered tumor DNA is still not quite sensitive enough for use yet,” he said.

Upping the sensitivity is just one of many hurdles scientists will have to clear before patients can choose bacteria over a colonoscopy.  Researchers will have to show engineered bacteria are safe to use and don’t alter the microbiome in a dangerous way, said Cooper. “And we might engineer an auto-destruct switch, so that when we’re done with them we can tell them to stop growing.”

Colon cancer is somewhat unique in that a few common mutations drive a good chunk of the disease. That’s not true for many other cancers, which stem from lots of rare mutations. “You wouldn’t want to rely solely on a system like this because there are sequences we might not know to look for,” said Cooper.

Still, researchers are just beginning to imagine possible uses for bacteria that can detect specific DNA sequences. “We might be able to detect infections with bacteria, DNA viruses or other microbes,” said Cooper. Or, scientists might be able to engineer tumor-detecting bacteria to also fight tumors, pairing early detection with early treatment.

“The field of synthetic biology is moving from doing things that are kind of neat to doing things that might be useful,” said Cooper.