In vivo evidence of metformin and aspirin antibacterial activity against Staphylococcus aureus in Drosophila infection model

Background: The significant increase in infectious bacterial diseases over the past two decades presents a serious global health threat, compounded by the limited efficacy of current therapeutic options. This has created an urgent need to explore novel antibacterial compounds. Traditional preclinical animal models used to evaluate drug candidates are often costly and require lengthy testing periods. The previous studies have shown Drosophila melanogaster to be an effective model organism for antibacterial drug discovery. In this study, we evaluated the in vivo antibacterial effects of metformin and aspirin against Staphylococcus aureus using a Drosophila infection model. Results: Our findings demonstrated that treatment with both metformin and aspirin significantly increased the survival of D. melanogaster infected with S. aureus. Additionally, both compounds inhibited bacterial growth in infected flies, as evidenced by reduced bacterial counts, indicating a direct antibacterial effect. Treatment also led to the downregulation of immune response-related genes, suggesting that the antibacterial activity occurred without immune system activation. Furthermore, metformin and aspirin reduced cell stress induced by bacterial infection, and these effects were validated in immunodeficient mutant flies, proving their efficacy independent of innate immune responses. Conclusion: These findings highlight the potential for repurposing metformin and aspirin as antibacterial agents. Using a high-throughput, cost-effective, and efficient Drosophila model, this study provides strong evidence supporting the viability of these compounds as treatments against bacterial infections.