Implementing Optogenetic-Controlled\nBacterial Systems\nin Drosophila melanogaster for Alleviation\nof Heavy Metal Poisoning

Drosophila melanogaster (fruit fly)\nis an animal model chassis in biological and genetic research owing\nto its short life cycle, ease of cultivation, and acceptability to\ngenetic modification. While the D. melanogaster chassis offers valuable insights into drug efficacy, toxicity, and\nmechanisms, several obvious challenges such as dosage control and\ndrug resistance still limit its utility in pharmacological studies.\nOur research combines optogenetic control with engineered gut bacteria\nto facilitate the precise delivery of therapeutic substances in D. melanogaster for biomedical research. We have\nshown that the engineered bacteria can be orally administered to D. melanogaster to get a stable density of approximately\n28,000 CFUs/per fly, leading to no detectable negative effects on\nthe growth of D. melanogaster. In a\nmodel of D. melanogaster exposure to\nheavy metal, these orally administered bacteria uniformly express\ntarget genes under green light control to produce MtnB protein for\nbinding and detoxifying lead, which significantly reduces the level\nof oxidative stress in the intestinal tract of Pb-treated flies. This\npioneering study lays the groundwork for using optogenetic-controlled\nbacteria in the model chassis D. melanogaster to advance biomedical applications.