Engineered probiotics for cancer detection

Danino et al. Programmable probiotics for detection of cancer in urine. Sci Transl Med. 2015 May 27; 7(289): 289ra84. doi: 10.1126/scitranslmed.aaa3519.

Scientists have used synthetic biology in an ingenious way to detect cancer in the urine. They took a harmless strain of E. coli that colonizes the liver and programmed it into an orally administered diagnostic device that can non-invasively indicate the presence of liver metastasis by producing a luminescent signal, detectable using simple urine test.

To turn this probiotic E. coli (Nissle 1917) into a diagnostic device, the scientists engineered the cells to express the LacZ reporter gene that cleaves lactose into glucose and galactose. They then fed mice these probiotic bacteria. Within 24 hours the probiotic translocated across the gastrointestinal tract and reached the metastatic tumors present in the liver. They then injected the mice with a substrate molecule that is broken down by the LacZ gene product. LacZ breaks down the substrate molecule, consisting of galactose linked to luciferin. Upon cleavage, luciferin is excreted in the urine where it is easily detected by a simple test.

But why didn't orally delivered bacteria accumulate in tumors all over the body – why liver specifically? Because the hepatic portal vein carries them from the digestive tract directly to the liver. The liver is also an ideal organ to target using oral delivery because it is the primary site of metastasis for several types of tumors including colorectal, breast and pancreatic tumors. The bacteria can selectively grow in tumors without adversely affecting host health due to suppressed immune surveillance within the tumor and increased availability of nutrients in the tumor core. This targeted ability of bacteria to selectively home to tumors also raises the possibility of using them as programmable drug delivery vehicles in the future.