A progesterone biosensor derived from microbial screening

Author:

Grazon ChloéORCID,Baer R C.,Kuzmanović Uroš,Nguyen Thuy,Chen MingfuORCID,Zamani Marjon,Chern MargaretORCID,Aquino Patricia,Zhang Xiaoman,Lecommandoux SébastienORCID,Fan Andy,Cabodi Mario,Klapperich Catherine,Grinstaff Mark W.ORCID,Dennis Allison M.,Galagan James E.ORCID

Abstract

AbstractBacteria are an enormous and largely untapped reservoir of biosensing proteins. We describe an approach to identify and isolate bacterial allosteric transcription factors (aTFs) that recognize a target analyte and to develop these TFs into biosensor devices. Our approach utilizes a combination of genomic screens and functional assays to identify and isolate biosensing TFs, and a quantum-dot Förster Resonance Energy Transfer (FRET) strategy for transducing analyte recognition into real-time quantitative measurements. We use this approach to identify a progesterone-sensing bacterial aTF and to develop this TF into an optical sensor for progesterone. The sensor detects progesterone in artificial urine with sufficient sensitivity and specificity for clinical use, while being compatible with an inexpensive and portable electronic reader for point-of-care applications. Our results provide proof-of-concept for a paradigm of microbially-derived biosensors adaptable to inexpensive, real-time sensor devices.

Funder

United States Department of Defense | Defense Advanced Research Projects Agency

U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences

Clare Booth Luce Graduate Fellowship Marie-Curie fellowship from the European Union under the program H2020

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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