Tenebrio molitor as an experimental model for comparing virulence profiles and immune response to pathogenic fungi of the genus Sporothrix
invertebrate model. antimicrobial peptides. infection. clinical clade. environmental clade. pathogenicity.
Diseases caused by pathogenic fungi have a substantial impact on both immunocompromised and immunocompetent patients, requiring lengthy treatments that, in some cases, demand hospitalization. In this regard, species and/or genotype-specific diagnosis can enhance disease prognosis, enabling a more targeted treatment depending on the etiological agent. Nevertheless, comparative studies on parasitism relationships involving closely related fungal species, often cryptic within the same genus, are still scarce. Species-specific virulence categorization directly impacts therapeutic direction and clinical prognosis, thereby optimizing case resolution. Consequently, the gold standard model for assessing the virulence of these pathogens is the murine model. However, currently, due to increased concerns about bioethical and financial issues, invertebrate animals have been proposed as attractive alternatives for infection models, given their innate immunity evolutionarily close to mammals, infrastructural ease, and robust data reproducibility. In this study, the virulence of different species of medical importance, from both clinical and environmental clades of the dimorphic fungus genus Sporothrix, as well as aspects of the innate immune response, were assessed in the invertebrate model Tenebrio molitor, in both the mycelial and yeast phases of the fungus. Thus, it was possible to compare virulence profiles and the host-parasite relationship among isolates of species within the genus. Significant differences were observed between the mycelial and yeast phases of pathogenic species from both Sporothrix clades. The species S. chilensis and S. pallida (environmental clade) demonstrated higher virulence in the mycelial morphology, whereas the species S. schenckii and S. brasiliensis (clinical clade) showed higher virulence in the yeast morphology. The expression of antimicrobial peptides (AMPs) from the invertebrate model was quantified, showing a significant difference in expression between groups infected with S. pallida and S. schenckii, indicating alterations in the pattern of the innate immune response concerning the Sporothrix species inoculated into the model.