Engineered live bacteria as disease detection and diagnosis tools

Sensitive and minimally invasive medical diagnostics are essential to the early detection of diseases, monitoring their progression and response to treatment. Engineered bacteria as live sensors are being developed as a new class of biosensors for sensitive, robust, noninvasive, and in situ detection of disease onset at low cost. Akin to microrobotic systems, a combination of simple genetic rules, basic logic gates, and complex synthetic bioengineering principles are used to program bacterial vectors as living machines for detecting biomarkers of diseases, some of which cannot be detected with other sensing technologies. Bacterial whole-cell biosensors (BWCBs) can have wide-ranging functions from detection only, to detection and recording, to closed-loop detection-regulated treatment. In this review article, we first summarize the unique benefits of bacteria as living sensors. We then describe the different bacteria-based diagnosis approaches and provide examples of diagnosing various diseases and disorders. We also discuss the use of bacteria as imaging vectors for disease detection and image-guided surgery. We conclude by highlighting current challenges and opportunities for further exploration toward clinical translation of these bacteria-based systems.