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A new experimental infection model in flies offers a fast and cost-effective way to test drugs
Researchers at the Germans Trias i Pujol Research Institute and Hospital have reinforced their leading role in infectious disease research by characterising and developing a new study model using Drosophila, which will enable the evaluation of various infectious agents.
The Clinical and Experimental Microbiology Unit (UMCiE) at the Germans Trias i Pujol Research Institute (IGTP), in collaboration with the Comparative Medicine and Bioimage Centre of Catalonia (CMCiB), a strategic project of the institute, has spent years studying and refining infection techniques in Drosophila melanogaster flies.
These organisms, commonly known as fruit flies, present multiple experimental advantages. They have a short life cycle, low maintenance costs, are easily genetically manipulated, and approximately 65% of their genes have human homologues, along with some shared physiological systems. Moreover, using Drosophila helps reduce the use of vertebrate animals in research, providing an ethical alternative for preliminary experiments.
UMCiE researchers are using D. melanogaster as an experimental model to evaluate new vaccines or antibiotics after demonstrating their efficacy in vitro (in the laboratory), before moving on to studies involving animals such as mice. Recently, they have published two articles in Frontiers in Microbiology and Frontiers in Immunology, leading journals in their respective fields, laying the groundwork for using this model for different infections and evaluating its innate immunity against infections by Candida albicans.
The Frontiers in Microbiology article outlines the establishment of the experimental infection model, reviewing a wide range of studies on the subject and detailing the research group's experience in this field. It describes all the techniques applicable, both for infection and drug administration, and how to evaluate them. The study encompasses the model for different infections and serves as the foundation for a platform that the group is developing to test new antibiotics.
In the other article, UMCiE scientists assess innate immunity against infections by Candida albicans, a yeast causing challenging-to-treat infections in immunocompromised patients. They have analysed the impact that enhanced immune response can have on the progression of highly virulent C. albicans infections. Paradoxically, although pre-immunisation can control yeast growth, it does not prevent the fly's death. This is due to an immune storm akin to what occurs in some patients with COVID-19.
Thus, the proposed Drosophila model also allows for the design of new therapeutic approaches that not only target pathogen destruction but also consider medications to control uncontrolled immune responses, known as "host-directed therapies". These could include anti-inflammatory drugs, corticosteroids, or other immunosuppressants.
Pere-Joan Cardona, leader of UMCiE at IGTP, head of the Microbiology Service at Germans Trias i Pujol University Hospital and CIBER of Respiratory Diseases (CIBERES) member, states: "These publications mark a significant milestone for the group in using the Drosophila infection model. We have established a platform where we can quickly and cost-effectively evaluate various candidates against infectious agents, whether they be antibiotics or immunomodulatory drugs. This aligns with CMCiB's mission to replace and reduce the use of laboratory animals like mice, representing a major achievement and positioning us as a reference group in this field".
About CMCiB
CMCiB is a cutting-edge facility specializes in interdisciplinary research at the intersection of comparative medicine and bioimaging. CMCiB's mission is to deepen our understanding of diseases, leveraging advanced bioimaging technologies, and translating research findings into innovative diagnostic and therapeutic approaches. Through collaborative efforts, CMCiB aims to contribute significantly to advancements in both human and animal health.
References
Vidal M, Arch M, Fuentes E, Cardona PJ. Drosophila melanogaster experimental model to test new antimicrobials: a methodological approach. Front Microbiol. 2024 Nov 6;15. DOI: 10.3389/fmicb.2024.1478263.
Cotacans M, Arch M, Fuentes E, Cardona PJ. Candida albicans infection model in Drosophila melanogaster suggests a strain-specific virulent factor boosting a stormy innate immune response. Front Immunol. 2024 Oct 31;15. DOI: 10.3389/fimmu.2024.1474516.
Funding
This research has been funded by Fundación "la Caixa" (ID 100010434), under agreement LCF/PR/GN16/10290002; the Government of Catalonia through AGAUR 2021 SGR 0931; and the Government of Spain with FEDER funds under project PI20/01431. It has also received funding from the European Commission for the ITHEMYC Project "Novel Immunotherapies for tuberculosis and other mycobacterial diseases", with grant agreement number 101080462.