科学美国人60秒:Programmed Bacteria Can Detect Tumors

Probiotics are hot. Bacteria that we consume in foods like yogurt, miso and pickles can help our gut microbiomes stay happy and healthy. Now there might be another role for those probiotic bacteria: cancer detection. Two papers in the journal Science Translational Medicine explain how researchers hope to get bacteria to be diagnostic tools. [Tal Danino et al, Programmable probiotics for detection of cancer in urine], [Alexis Courbet et al, Detection of pathological biomarkers in human clinical samples via amplifying genetic switches and logic gates]

Sangeeta Bhatia of MIT is a liver expert and senior author of one of the papers. Her lab had been trying to figure out how to get nanoparticles to the liver that would send a signal detectable in urine if they encountered a tumor. Cancers that start in the colon or pancreas can metastasize to the liver, which can be deadly.

SB: “And one of the students on the team had the idea that if you can imagine that there's a material, a diagnostic material, that would grow itself then you wouldn’t need very much of it to arrive at the tumor and sort of self-amplify. And we realized that bacteria are in many ways just such a device. That they can naturally home in on tumors…so we thought maybe we can hijack that ability of bacteria to home in on tumors and self-amplify to create a urinary diagnostic.”

Bhatia’s lab teamed up with a lab at the University of California, San Diego with expertise in synthetic biology—basically altering microbes to have specific functions.

SB: “So instead of just going out and finding natural strains that would colonize tumors and do what wanted, we could pick strains that have good homing and then endow them with the capabilities that we were interested in.”

The two labs took a strain of E. coli called Nissle that is already used as a probiotic to help people with digestive issues. They programmed the bacteria to express a specific enzyme after it occupied liver tumors. If the bacteria colonized a tumor in mice, the mice would produce urine that, thanks to the enzyme, would turn red.

The system worked—the bacteria found tumors in mice known to have them, and the urine changed color, indicating the presence of cancer. Cancer-free mice that also ate the engineered probiotics showed no negative health effects a year later.

The technique is at this stage just a proof of concept, says Bhatia. But it’s got a lot of promise.

SB: “Well what we're really excited about the idea that you can take synthetic biology some day into both diagnostics and also therapeutics. So in this particular case the circuit that we put the bacteria gave off a diagnostic signal that could be detected remotely. But you can also imagine and were working on circuits that give off chemotherapy that would kill the tumor directly. And making smart circuits do that in response of ways. And you can even imagine having mixtures of bacteria that do both diagnosis and therapy. So I think there's really a whole world of possibilities once you start thinking about using bacteria as a platform upon which to engineer functions.”

—Cynthia Graber

(The above text is a transcript of this podcast)