Programmable receptors enable bacterial biosensors to detect pathological biomarkers in clinical samples

Abstract Bacterial biosensors, or bactosensors, are promising agents for medical and environmental diagnostics. However, the lack of scalable frameworks to systematically program ligand detection limits their applications. Here we show how novel, clinically relevant sensing modalities can be introduced into bactosensors in a modular fashion. To do so, have leveraged synthetic receptor platform, termed EMeRALD (Engineered Modularized Receptors Activated via Ligand-induced Dimerization) which supports assembly modules onto high-performance, generic signaling scaffold controlling gene expression E. coli . We apply detect bile salts, biomarker liver dysfunction, by repurposing from enteropathogenic Vibrio species. improve sensitivity lower limit-of-detection module directed evolution. then engineer colorimetric bactosensor detecting pathological salt levels serum patients having undergone transplant, providing an output detectable naked-eye. The technology enables functional exploration natural rapid engineering receptors diagnostics, monitoring, control therapeutic microbes.