Engineered bacteria detect tumor DNA

Summary

Advances in bacterial engineering have catalysed the development of living cell diagnostics and therapeutics^1–3, including microbes that respond to gut inflammation⁴, intestinal bleeding⁵, pathogens⁶ and hypoxic tumors⁷. Bacteria can access the entire gastrointestinal tract⁸ to produce outputs measured in stool⁴ or urine⁷. Cellular memory, such as bistable switches^4,9,10 or genomic rearrangements¹¹, allows bacteria to store information over time. However, living biosensors have not yet been engineered to detect specific DNA sequences or mutations from outside the cell. Here, we engineer naturally competent Acinetobacter baylyi to detect donor DNA from the genomes of colorectal cancer (CRC) cells, organoids and tumors. We characterize the functionality of the biosensors in vitro with co-culture assays and then validate in vivo with sensor bacteria delivered to mice harboring colorectal tumors. We observe horizontal gene transfer from the tumor to the sensor bacteria in our mouse model of CRC. The sensor bacteria achieved 100% discrimination between mice with and without CRC. This Cellular Assay of Targeted, CRISPR-discriminated Horizontal gene transfer (CATCH), establishes a framework for biosensing of mutations or organisms within environments that are difficult to sample, among many other potential applications. Furthermore, the platform could be readily expanded to include production and delivery of antibiotic or antineoplastic therapeutic payloads at the detection site.