Development of a Transcriptional Biosensor for Hydrogen Sulfide That Functions under Aerobic and Anaerobic Conditions.

Hydrogen sulfide (HS) is a gaseous gut metabolite with disputed effects on gastrointestinal health. Monitoring HS concentration in the gut would provide insight into its role in disease but is complicated by sulfide's reactivity and volatility. Here we develop a transcriptional sulfide biosensor in . The sensor relies on enzymatic oxidation of sulfide catalyzed by a sulfide:quinone oxidoreductase (Sqr) to polysulfides, which interact with the repressor SqrR, triggering unbinding from the promoter and transcription of the reporter. Through promoter engineering and improved soluble SqrR expression, we optimized the system to provide an operational range of 50-750 μM and a dynamic range of 18 aerobically. To enable sensing in anaerobic environments, we identified an Sqr from that uses menaquinone, facilitating reoxidation through the anaerobic electron transport chain by fumarate or nitrate. Use of this homologue resulted in an anaerobic HS response up to 750 μM. This sensor could ultimately enable spatially and temporally resolved measurements of HS in the gastrointestinal tract to elucidate the role of this metabolite in disease and potentially as a noninvasive diagnostic.