In vivo Fusarium virulence and efficacy of voriconazole in a Galleria mellonella model of invasive fusariosis

Fusarium species are transkingdom pathogens involved in invasive fungal infections in immunocompromised patients. Despite high minimum inhibitory concentrations (MICs), voriconazole (VRZ) is the antifungal recommended as a first-line treatment for this infection.

The objective of this study was to use larvae of the invertebrate Galleria mellonella to describe invasive Fusarium infection, evaluate the virulence profiles of a set of strains and determine the response of Fusarium to antifungal treatment.

After characterization of the fungal infection in G. mellonella threw histological analysis, fungal burden by qPCR and hemocyte counts, larval survival was evaluated after injection of Fusarium solani species complex (FSSC) conidia, with or without therapeutic VRZ injection.

In the described model, an increase in fungal burden was observed in relation to the inoculum size and duration of infection, which was associated with an increase in hemocyte counts. Histopathological examination revealed the invasive nature of the filamentous fungus, along with a nodulation process at the highest inoculum concentrations. Mortality and consequently virulence varied according to the strains under investigation. However, a subgroup analysis by VRZ MIC and strain origin revealed slightly increased mortality for the strains most susceptible to VRZ, as well as for the strains of clinical origin in infected larvae. In this model, VRZ presented in vivo activity and post-infection treatment decreased larval mortality.

The originality of this study lies in the integrated use of the invertebrate model G. mellonella, which is not employed solely for survival analysis, but comprehensively as an in vivo model of invasive fungal infection, with infection monitoring performed through multiple technical approaches.