Abstract
Dimorphic fungi can be found in the yeast form during infection and as hyphae in the environment and are responsible for a large number of infections worldwide. Invertebrate animals have been shown to be convenient models in the study of fungal infections. These models have the advantages of being low cost, have no ethical issues, and an ease of experimentation, time-efficiency, and the possibility of using a large number of animals per experiment compared to mammalian models. Invertebrate animal models such as Galleria mellonella, Caenorhabditis elegans, and Acanthamoeba castellanii have been used to study dimorphic fungal infections in the context of virulence, innate immune response, and the efficacy and toxicity of antifungal agents. In this review, we first summarize the features of these models. In this aspect, the growth temperature, genome sequence, availability of different strains, and body characteristics should be considered in the model choice. Finally, we discuss the contribution and advances of these models, with respect to dimorphic fungi Paracoccidioides spp., Histoplasma capsulatum, Blastomyces dermatitidis, Sporothrix spp., and Talaromyces marneffei (Penicillium marneffei).
Highlights
Use of animal experimentation for both scientific and medical areas of research is a fundamental step for validating in vitro results and understanding different processes in a complex organism [1].Since 1959, the “3 Rs” principle suggested by Russell andBurch has been used to demonstrate concern regarding the ethical issues and animal welfare during animal experimentation
Activation of antimicrobial pathways, such as mitogen-activated protein kinases (MAPKs) and transforming growth factor β (TGF-β), production of reactive oxygen species (ROS), and secretion of antimicrobial molecules occurs in a similar manner between worms and mammals against fungi and bacteria [53,54,55,56]
In the infection with yeast-like cells, which is the form associated with the disease, a significant increase in the mortality rate due to infection with S. brasiliensis was observed when compared with S. schenckii sensu stricto, suggesting that S. brasiliensis is more virulent in G. mellonella, as previously observed in a murine model [31,115]
Summary
Use of animal experimentation for both scientific and medical areas of research is a fundamental step for validating in vitro results and understanding different processes in a complex organism [1]. The scientific society has developed different methodologies to apply the 3 Rs principles such as in silico analysis, cell and tissue culture, and invertebrate animal models [2] Invertebrates such as Galleria mellonella, Caenorhabditis elegans, and Acanthamoeba castellanii have been successfully used for in vivo assays, including in the study of dimorphic fungi. These models are easier to develop, time-efficient, cost-efficient, and offer the possibility of using a large number of animals per experiment compared to mammalian models [10,11]. This review describes the features and advances in the use of invertebrate animal models in order to study dimorphic fungal infections
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