A synthetic receptor platform enables rapid and portable monitoring of liver dysfunction via engineered bacteria.

Chang, H.-J.; Zuniga, A.; Conejero, I.; Voyvodic, P. L.; Gracy, J.; Fajardo-Ruiz, E.; Cohen-Gonsaud, M.; Cambray, G.; Pageaux, G.-P.; Meszaros, M.; Meunier, L.; Bonnet, J.

doi:10.1101/2021.03.24.436753

bioRxiv · 10.1101/2021.03.24.436753

A synthetic receptor platform enables rapid and portable monitoring of liver dysfunction via engineered bacteria.

Chang, H.-J.·Zuniga, A.·Conejero, I.·Voyvodic, P. L.·Gracy, J.·Fajardo-Ruiz, E.·Cohen-Gonsaud, M.·Cambray, G.·Pageaux, G.-P.·Meszaros, M.·Meunier, L.·Bonnet, J.

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Abstract

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

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Chang, H.-J., Zuniga, A., Conejero, I., Voyvodic, P. L., Gracy, J., Fajardo-Ruiz, E., Cohen-Gonsaud, M., Cambray, G., Pageaux, G.-P., Meszaros, M., Meunier, L., Bonnet, J.. 2021-03-29. A synthetic receptor platform enables rapid and portable monitoring of liver dysfunction via engineered bacteria.. https://doi.org/10.1101/2021.03.24.436753

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