Model of Coccidioidomycosis for Drug Susceptibility Tests and Virulence Factor Identification.

Coccidioidomycosis (CM) can manifest as respiratory and disseminated diseases that are caused by dimorphic fungal pathogens, such as species. The inhaled arthroconidia generated during the saprobic growth phase convert into multinucleated spherules in the lungs to complete the parasitic lifecycle. Research on coccidioidal virulence and pathogenesis primarily employs murine models typically associated with low lethal doses (LD < 100 spores). However, the model has recently garnered attention due to its immune system bearing both structural and functional similarities to the innate system of mammals. Our findings indicate that can convert and complete the parasitic cycle within the hemocoel of the larva. In , the LD is between 0.5 and 1.0 × 10 viable spores for the clinical isolate C735. Furthermore, we demonstrated the suitability of this model for in vivo antifungal susceptibility tests to validate the bioreactivity of newly discovered antifungals against . Additionally, we utilized this larva model to screen a mutant library showing attenuated virulence. Similarly, the identified attenuated coccidioidal mutants displayed a loss of virulence in a commonly used murine model of coccidioidomycosis. In this study, we demonstrated that larvae can be applied as a model for studying infection.