Caenorhabditis elegans-Based Aspergillus fumigatus Infection Model for Evaluating Pathogenicity and Drug Efficacy

Abstract

<i>Aspergillus fumigatus</i> is the most reported causative pathogen associated with the increasing global incidences of aspergilloses, with the health of immunocompromised individuals mostly at risk. Monitoring the pathogenicity of <i>A. fumigatus</i> strains to identify virulence factors and evaluating the efficacy of potent active agents against this fungus in animal models are indispensable in current research effort. <i>Caenorhabditis elegans</i> has been successfully utilized as an infection model for bacterial and dimorphic fungal pathogens because of the advantages of being time-efficient, and less costly. However, application of this model to the filamentous fungus <i>A. fumigatus</i> is less investigated. In this study, we developed and optimized a stable and reliable <i>C. elegans</i> model for <i>A. fumigatus</i> infection, and demonstrated the infection process with a fluorescent strain. Virulence results of several mutant strains in our nematode model demonstrated high consistency with the already reported pathogenicity pattern in other models. Furthermore, this <i>C. elegans-A. fumigatus</i> infection model was optimized for evaluating the efficacy of current antifungal drugs. Interestingly, the azole drugs in nematode model prevented conidial germination to a higher extent than amphotericin B. Overall, our established <i>C. elegans</i> infection model for <i>A. fumigatus</i> has potential applications in pathogenicity evaluation, antifungal agents screening, drug efficacy evaluation as well as host-pathogen interaction studies.