Implementing Optogenetic-Controlled Bacterial Systems in <i>Drosophila melanogaster</i> for Alleviation of Heavy Metal Poisoning

<i>Drosophila melanogaster</i> (fruit fly) is an animal model chassis in biological and genetic research owing to its short life cycle, ease of cultivation, and acceptability to genetic modification. While the <i>D. melanogaster</i> chassis offers valuable insights into drug efficacy, toxicity, and mechanisms, several obvious challenges such as dosage control and drug resistance still limit its utility in pharmacological studies. Our research combines optogenetic control with engineered gut bacteria to facilitate the precise delivery of therapeutic substances in <i>D. melanogaster</i> for biomedical research. We have shown that the engineered bacteria can be orally administered to <i>D. melanogaster</i> to get a stable density of approximately 28,000 CFUs/per fly, leading to no detectable negative effects on the growth of <i>D. melanogaster</i>. In a model of <i>D. melanogaster</i> exposure to heavy metal, these orally administered bacteria uniformly express target genes under green light control to produce MtnB protein for binding and detoxifying lead, which significantly reduces the level of oxidative stress in the intestinal tract of Pb-treated flies. This pioneering study lays the groundwork for using optogenetic-controlled bacteria in the model chassis <i>D. melanogaster</i> to advance biomedical applications.