Virulence on the Fly: Drosophila melanogaster as a Model Genetic Organism to Decipher Host-Pathogen Interactions

Abstract

To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens might not develop resistance easily. Model organisms are a useful tool for this endeavor, thanks to the power of their genetics. Drosophila melanogaster is widely used to study host-pathogen interactions. Its basal immune response is well understood and is briefly reviewed here. Considerations relevant to choosing an adequate infection model are discussed. This review then focuses mainly on infections with two categories of pathogens, the well-studied Gram-negative bacterium Pseudomonas aeruginosa and infections by fungi of medical interest. These examples provide an overview over the current knowledge on Drosophila-pathogen interactions and illustrate the approaches that can be used to study those interactions. We also discuss the usefulness and limits of Drosophila infection models for studying specific host-pathogen interactions and high-throughput drug screening.

Insects emerge as valuable model hosts to explore virulence

“…4 Therefore, insects such as the fruit fly Drosophila melanogaster attract increasing attention as models to decipher host-pathogen interactions since its genome sequence and mutant libraries have become available. [5][6][7] The latter have been used, for example, to show that Toll-deficient strains are both resistant to infection by human pathogenic fungi belonging to Pneumocystis spp, 8 and promising as models for studying pathogenesis of Aspergillus fumigatus and testing of drugs against aspergillosis. 9 However, research on insect model hosts lacked for a long time acceptance by clinicians and clinical researchers due to skepticism about the transferability of the elaborated knowledge.…”

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“…Recently Drosophila melanogaster has been recognized as a model system to study microbial pathogenicity 12,13,[23][24][25][26] . Its fast growth, short life cycle, ease of manipulation, low cost and simplicity of ethical and regulatory issues, make it an attractive host for such studies, and its immune system is similar in some ways to the mammalian innate immune system 12,23,24,27,28 .…”

“…Its fast growth, short life cycle, ease of manipulation, low cost and simplicity of ethical and regulatory issues, make it an attractive host for such studies, and its immune system is similar in some ways to the mammalian innate immune system 12,23,24,27,28 .…”

“…flavus produces severe systemic infection in flies, probably affecting internal organs and others parts of the body 13 . Fungal dissemination throughout different organs begins with invasion or inhalation of A. flavus spores, which may involve particular virulence routes such as interaction of the fungus with epithelial receptors and colonization of the digestive tract 23 . A. flavus is not host-specific, and is capable of causing disease in humans, plants, and insects 34 .…”

The multilayered innate immune defense of the gut

“…Understanding of the antimicrobial responses in the Drosophila gut has been advanced by the development of oral infection models, [1][2][3][4][5][6][7][8] studies of gut structure, [3,[9][10][11][12][13][14][15][16][17][18][19][20] characterization of commensal microbiota, [6,[21][22][23][24][25][26] and use of axenic flies. [27][28][29][30] These studies reveal that the basal immune response is weakly induced by the commensal gut microbes and strongly enhanced upon pathogen immune challenge.…”