P19
Evolution of resistance and tolerance of Drosophila melanogaster after infection with Mycobacterium marinum. Impact of sex and contact with killed rapid growing Mycolicibacterium
M Arch(1,2,3,5) M Vidal(1,2,5) E Fuentes(1,2,4,5) P J Cardona(1,2,3,4,5)
1:Comparative Medicine and Bioimage Centre of Catalonia (CMCiB), Germans Trias i Pujol Research Institute (IGTP); 2:Experimental Tuberculosis Unit, Germans Trias i Pujol Research Institute (IGTP); 3:Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES); 4:Microbiology Department, North Metropolitan Clinical Laboratory, ‘Germans Trias i Pujol’ University Hospital; 5:Genetics and Microbiology Department, Universitat Autònoma de Barcelona
The Mycobacterium marinum (Mm) infection in Drosophila melanogaster (Dm) has shown to be a good experimental model of TB. It has provided an important insight on the innate immunity response, as insects rely solely on this type of response thus avoiding the variability that adaptive mechanisms imply. Also due to the high homology of the genes that determine it with humans: approximately sharing a 75% of genetical homology. We have use it to evaluate the pathogen-host coevolution for 10 generations, taking into account the sex and the oral administration of heat killed Mycolicibacterium manresensis (hkMm), a rapid growing mycobacteria. Flies were divided into 4 groups: flies injected with PBS; orally treated with hkMm and injected with PBS, flies infected with 500CFU of Mm, and flies that combined infection and treatment. After 12 days of infection, survived flies were transferred for mating for 24 hours to develop the next generation and Mm from survival flies was also recovered to be used to infect the next generation. Differential expression analysis and Gene Set Enrichment analysis (GSEA) was performed at generations 0 and 5, 24h and 10 days post infection. Data show an increase of resistance against coevolved Mm infection. This is based on an increased oxidative stress in response to Mm in males and increased endocytic activity in females. Oral administration of hkMm increases both tolerance and resistance against coevolved Mm in both sexes through the up-regulation of genes related with reduction of cachexia and increased humoral response.