P115

1:Unitat de Tuberculosi Experimental, Microbiology Dept. Germans Trias i Pujol Research Institute and Hospital (IGTP-HUGTIP), Badalona, 08916, Spain; 2:Genetics and Microbiology Department, Autonomous University of Barcelona, Barcelona, 08193, Spain; 3:Centre de Medicina Comparativa i Bioimatge de Catalunya (CMCiB), Badalona, 08916, Spain; 4:Servei de Microbiologia, LCMN, Hospital Universitari Germans Trias i Pujol (HUGTiP), Badalona, 08916, Spain; 5:Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, 28029, Spain

Antimicrobial-resistant infections are an escalating public health issue, underscoring the urgent need for new drug discovery. Current methods often rely on in vitro cell cultures, resulting in many low-quality compounds progressing to mammal models. D. melanogaster (Dm) is a valuable model for studying host-pathogen interactions and treatment efficacy. Acting as a bridge between in vitro and mammal models, Dm may overcome the time and cost challenges of drug screening. However, further refinements are needed to establish it as a standard tool in this process. In this study, we validated a cost-effective treatment protocol using Dm infected with Mycobacterium marinum (Mm). We tested five standard tuberculosis drugs, the current standard of care; five repurposed host-directed therapies; and two anti-virulence treatments. Flies were systematically infected with 50 Colony Forming Units (CFUs) of Mm and orally treated with a mixture of each compound in a yeast paste on day 3 post-infection (p.i.), after the infection was established. The treatment lasted 7 days, with survival monitored daily and bacillary load measured at days 3 and 10 p.i. By day 10, treated flies showed significantly higher survival rates and reduced bacillary load than controls, except for pyrazinamide, isoniazid, and doramapimod-treated flies, possibly due to the model's physiological characteristics. In conclusion, this study validates the Dm infection model as proof of concept for drug screening, offering a cost-effective method while acknowledging the limitations for those compounds that need to be metabolized inside flies and those with structural targets not present in D. melanogaster.