Engineered bacteria detect tumor DNA in vivo

In vitro nucleic acid analysis has become a valuable diagnostic tool. However, in vitro measurements have many disadvantages when compared to in vivo techniques. Synthetic bacterial biosensors have been engineered to sense many target signals in vivo, but no biosensor exists to detect specific DNA sequences. Here, we engineered naturally competent Acinetobacter baylyi bacteria to detect engineered donor DNA inserted into the genomes of colorectal cancer (CRC) cells and organoids. The DNA biosensor concept was developed in vitro and then validated in vivo with sensor bacteria delivered orally or rectally to mice that had been injected with orthotopic donor CRC organoids. Horizontal gene transfer occurred from the donor tumor to the sensor bacteria in vivo, conferring antibiotic resistance to the sensor bacteria and allowing their detection in stool. The sensor bacteria differentiated mice with and without CRC. Life detecting life has many implications for future diagnosis, prevention, and treatment of disease. This approach may also be useful in any application that requires the detection of mutations or organisms within environments that are difficult to sample.