title: Drosophila melanogaster as a model for elucidating the pathogenicity of Francisella tularensis.
abstract: Drosophila melanogaster is a widely used model organism for research on innate immunity and serves as an experimental model for infectious diseases. The aetiological agent of the zoonotic disease tularaemia, Francisella tularensis, can be transmitted by ticks and mosquitoes and Drosophila might be a useful, genetically amenable model host to elucidate the interactions between the bacterium and its arthropod vectors. We found that the live vaccine strain of F. tularensis was phagocytosed by Drosophila and multiplied in fly haemocytes in vitro and in vivo. Bacteria injected into flies resided both inside haemocytes and extracellularly in the open circulatory system. A continuous activation of the humoral immune response, i.e. production of antimicrobial peptides under control of the imd/Relish signalling pathway, was observed and it may have contributed to the relative resistance to F. tularensis as flies defective in the imd/Relish pathway died rapidly. Importantly, bacterial strains deficient for genes of the F. tularensis intracellular growth locus or the macrophage growth locus were attenuated in D. melanogaster. Our results demonstrate that D. melanogaster is a suitable model for the analysis of interactions between F. tularensis and its arthropod hosts and that it can also be used to identify F. tularensis virulence factors relevant for mammalian hosts.
authors.affiliation: Department of Clinical Microbiology, Umeå University, 90185 Umeå, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Vonkavaara
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Telepnev
authors.forename: Patrik
authors.initials: P
authors.lastname: Rydén
authors.forename: Anders
authors.initials: A
authors.lastname: Sjöstedt
authors.forename: Svenja
authors.initials: S
authors.lastname: Stöven
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000276:immunology / Q000382:microbiology*; D005604:Francisella tularensis / Q000254:growth & development / Q000472:pathogenicity; D017344:Genes, Insect / Q000235:genetics; D006434:Hemocytes / Q000382:microbiology; D007113:Immunity, Innate; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014406:Tularemia / Q000378:metabolism* / Q000382:microbiology*; D014774:Virulence
chemical_list: D029721:Drosophila Proteins; D010455:Peptides; C101626:Rel protein, Drosophila; D014157:Transcription Factors; C439909:imd protein, Drosophila