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Mycobacterium tuberculosis infecting Drosophila melanogaster: first insights of the new latent tuberculosis infection model.

M Vidal(1,2,3) P Soldevilla(1,2,3,4) M Arch(1,3) E Fuentes(1,3) J Díaz(3) P J Cardona(1,2,3,4)

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:Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, 28029, Spain

Latent tuberculosis infection (LTBI) affects a quarter of the world population, with a 5-15% risk of progression to active tuberculosis (ATB). LTBI and ATB harbour dormant Mycobacterium tuberculosis, whose low metabolic activity implies the administration of complex treatments with low adherence, favouring antibiotic resistance acquisition. Therefore, the search for new therapeutic strategies against dormant bacilli is essential to control TB. Drosophila melanogaster is a suitable animal model to evaluate the therapeutic efficacy of a wide variety of compounds. This has been demonstrated with Mycobacterium marinum and Mycobacterium abscessus infections. However, there is a lack of a Mtb infection model in D. melanogaster. We hypothesize that, as D. melanogaster grows at 25ºC, it will keep Mtb infection in dormant status. Hence, we want to establish a model of LTBI in D. melanogaster for the characterization of the pathogenic mechanism of the infection and the evaluation of new therapeutic strategies. After setting up the equipment for working with D. melanogaster in Biological Safety Level 3 (NSB3) facilities, we performed Mtb infections with different doses. We monitored the survival daily and measured bacillary load at different times post-infection. Our results showed no significant difference in survival rates between the control and infected groups. Nevertheless, the infection is maintained over time. Although the model is still being optimized for use in NSB3 facilities and for the establishment of a suitable procedure to assess bacillary load within the host, it will constitute an extraordinary tool for the study of new therapeutic strategies against dormant Mtb.

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