Programmable Probiotics Detect Cancer in Urine

Rapid advances in the forward engineering of genetic circuitry in living cells has positioned synthetic biology as a potential means to solve numerous biomedical problems, including disease diagnosis and therapy.

A new way has been devised to detect cancer that has spread to the liver, by enlisting help from probiotics, those beneficial bacteria similar to those found in yogurt. A harmless strain of Escherichia coli that colonizes the liver has been programmed so that the bacteria produce a luminescent signal that can be detected with a simple urine test.


Bioengineers at the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA) and their colleagues used a murine model and engineered a harmless strain of E. coli to express the gene for a naturally occurring enzyme called lacZ that cleaves lactose into glucose and galactose. In this case, lacZ acts on a molecule injected into the mice, consisting of galactose linked to luciferin, a luminescent protein naturally produced by fireflies. Luciferin is cleaved from galactose and excreted in the urine, where it can easily be detected using a common laboratory test.

The urine was tested for luciferin with the QuantiLum Recombinant Luciferase Kit (Promega; Madison, WI, USA) via luminescence in a Centro LB 960 Universal Microplate Luminometer (Berthold; Bad Wildbad, Germany). In tests with mice, the scientists found that orally delivered bacteria do not accumulate in tumors all over the body, but they do predictably zero in on liver tumors because the hepatic portal vein carries them from the digestive tract to the liver. This allowed the team to develop a diagnostic specialized for liver tumors. In tests in mice with colon cancer that has spread to the liver, the probiotic bacteria colonized nearly 90% of the metastatic tumors.

Sangeeta N. Bhatia, MD, PhD, a professor of health sciences and senior author of the study, said, “We realized that if we gave a probiotic, we weren't going to be able to get bacteria concentrations high enough to colonize the tumors all over the body, but we hypothesized that if we had tumors in the liver they would get the highest dose from an oral delivery.” The study was published on May 27, 2015, in the journal Science Translational Medicine.

Related Links:
Massachusetts Institute of Technology 
Promega 
Berthold