Nhu Nguyen, Miaomiao Wang, Sithembiso S Msibi, Vincenzo Kennedy, Fateme Esmailie, L Joseph Su, Lin Li, Clement T Y Chan
Chronic exposure to arsenite in food and water is a major global health concern, yet no practical strategies exist to prevent ingested arsenite from entering the body through the gastrointestinal tract. Here, we engineered Escherichia coli Nissle 1917 (EcN) to sense and sequester arsenite in situ, creating a probiotic-based approach to reduce host absorption of arsenite. The system involved an arsenite-responsive genetic toggle switch that activated chelator expression upon exposure; after arsenite was removed, it sustained output under biostatic conditions but shut off during active cell division. We also engineered a nontoxic, high-affinity arsenite-binding protein as the chelator. The resulting strain efficiently removed arsenite in vitro while maintaining robust growth. A mass-transfer model guided in vivo dosing, and mouse studies showed that engineered EcN reduced arsenite entry into the bloodstream and promoted its fecal elimination. These findings support the conclusion that this engineered probiotic approach is promising for addressing toxic pollutants in the diet.