Fluorescent-glowing bacteria help scientists see inside the body’s ‘dark places’

In this photo of E.coli bacteria, some have been genetically engineered to contain red fluorescent proteins that aren't passed on to the next generation, allowing scientists to track the death and reproduction of bacteria in the gut.
In this photo of E.coli bacteria, some have been genetically engineered to contain red fluorescent proteins that aren't passed on to the next generation, allowing scientists to track the death and reproduction of bacteria in the gut.

The average person carries trillions of bacteria, fungi, protozoa, and other microbes around in their body, outnumbering their human cells by what has been estimated to be a ratio of 10 to 1.

These tiny partners can play a crucial role in our health, helping to digest food and ward off infection.

But since we can’t see inside one of the body’s greatest microbe hotspots — the gut — it’s hard to say exactly what happens to those organisms once they enter the digestive tract.

Now, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University say they’ve found a new way of counting those microbes by rewiring the organisms’ DNA to give off a fluorescent glow.

Their work could eventually help scientists analyze how antibiotics affect bacteria inside the body, or help companies that rely on microbes, such as beer-makers and ethanol producers, better understand what makes microorganisms thrive.

“This is a way of exploring in what I call ‘dark places,’ ” said Pam Silver, a biologist at the Wyss Institute.

The research, reported in the Nov. 30 edition of Nature Communications, was led by graduate fellow Cameron Myhrvold. The project started with a bundle of E.coli bacteria genetically engineered to include a red fluorescent protein, making them easy to identify under the microscope.

Those glowing particles, however, couldn’t be passed on to the next generation of microbes once the bacterial cells divided. So after one generation, you would expect half of the bacteria to glow red.

The researchers fed these red-fluorescent bacteria to lab mice, and collected their feces to count how many of the E.coli made it all the way through the system.

By seeing what proportion of the final sample had red-colored bacteria, the scientists could effectively “count” how many generations had been produced inside the mice’s gut.

Using genetically modified bacteria or other microbes in a human subject is still far off in the future, the researchers cautioned. But the ability to “watch” what happens to important microorganisms in volatile spots inside the body could be a big leap forward from analyzing antibiotics or probiotics strictly in the lab, Myhrvold said.

“If you wanted to test a new compound, this would be a very good way to do that inside the gut — because you could tell how that compound was affecting the bacterium inside the gut, not just in a culture,” he said.