Fig. 1: Concept of probiotic biosensors for ultrasound imaging of gastrointestinal (GI) inflammation.

Patients consume yogurt containing diagnostic probiotic bacteria that transiently populate the GI tract. Using two-component systems (TCSs), these engineered bacteria sense inflammatory biomarkers, such as thiosulfate and tetrathionate, and express acoustic reporter genes (ARGs) that encode for gas vesicles (GVs) in response. Binding of the biomarker to the membrane sensor kinase protein triggers transcription of ARGs from a specific promoter via phosphorylation of a cytoplasmic response regulator protein; in the absence of the biomarker, phosphatase activity of the membrane sensor kinase keeps the system repressed. ARG-expressing bacteria can be detected via ultrasound imaging in patients, enabling ultrasound imaging of GI inflammation.