Mycobacterium marinum infection in Drosophila melanogaster for antimycobacterial activity assessment.

OBJECTIVES: The major advantages of Drosophila melanogaster are a well-characterized immune system and high degree of susceptibility to tuberculosis caused by Mycobacterium marinum. The D. melanogaster-M. marinum infection model is gaining momentum as a screening tool because it is genetically amenable, low priced, rapid, technically convenient and ethically acceptable. In this context, the aim of this study was to develop a new, effective D. melanogaster-M. marinum in vivo efficacy model for antimycobacterial drug discovery.
METHODS: D. melanogaster were challenged with intra-abdominal injections of M. marinum and infected flies were fed with a fly medium containing isoniazid, rifampicin, ethambutol, pyrazinamide, amikacin, dinitrobenzamide or ampicillin dissolved in DMSO at different concentrations (0, 100 and 500 mg/L). Bacterial dissemination in flies was monitored by fluorescence microscopy/cfu counts and a fly survival curve was plotted.
RESULTS: The D. melanogaster-M. marinum model allowed assessment of the effectiveness of antibiotic treatment not only with conventional drugs, but also with newly discovered antimycobacterial agents. Rifampicin, dinitrobenzamide, amikacin and isoniazid effectively extended the life span of infected flies and ethambutol showed slightly improved survival. However, M. marinum infection was not cured by ampicillin or pyrazinamide.
CONCLUSIONS: This D. melanogaster-M. marinum infection/curing methodology may be valuable in the rapid evaluation of the activity of new antimycobacterial agents in drug discovery.