Drosophila melanogaster as a experimental model for infectious diseases

Drosophila melanogaster (Dm) relies solely on innate immunity to defend against infections, with hemocytes (precursors of human macrophages) mediating cellular responses and antimicrobial peptides driving humoral defenses. Its minimal redundancy in effector pathways makes Dm a simplified yet holistic model for studying immune, metabolic, and humoral interactions, as well as tolerance and resistance to infections. Resistance denotes the host’s ability to eliminate pathogens, while tolerance reflects its capacity to endure infection without compromising health.
We present two examples utilizing Dm. First, we studied host-pathogen coevolution in the context of tuberculosis using Mycobacterium marinum (Mm). Over ten generations, flies were reinfected with pathogens isolated from their cohorts, and some were exposed to heat-inactivated Mycolicibacterium manresensis (hkMm) to evaluate the influence of environmental mycobacteria. At generations 5 and 10, tolerance and resistance assays revealed whether host-pathogen coevolution altered Mm virulence, with non-coevolved flies as controls.
Second, we examined infection by Candida albicans. A clinical yeast strain proved highly virulent (causing mortality within 2 days), while a reference strain allowed survival beyond 20 days. Immune priming with heat-killed C. albicans(hkCa) or hkMm enhanced resistance by suppressing yeast growth but did not improve tolerance, as excessive immune activation drove mortality.
Lastly, we highlight a Dm-based platform for antibiotic screening, providing robust preclinical data while reducing reliance on murine models. This aligns with the 3Rs principle, particularly in replacement, supporting initiatives at the Comparative Medicine and Bioimaging Center of Catalonia (CMCiB) at the Germans Trias i Pujol Research Institute (IGTP).