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

Chukwuemeka Samson Ahamefule,Cheng Jin,James C Ogbonna,Arome Solomon Odiba,Bin Wang,Anene N Moneke,Qijian Qin,Siqiao Li,Wenxia Fang

doi:10.3389/fcimb.2020.00320

Abstract

Aspergillus fumigatus 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 A. fumigatus 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. Caenorhabditis elegans 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 A. fumigatus is less investigated. In this study, we developed and optimized a stable and reliable C. elegans model for A. fumigatus 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 C. elegans-A. fumigatus 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 C. elegans infection model for A. fumigatus has potential applications in pathogenicity evaluation, antifungal agents screening, drug efficacy evaluation as well as host-pathogen interaction studies.

Highlights

Aspergillus fumigatus is a saprophytic environmental fungus with ubiquitous airborne spores
C. elegans has been successfully utilized as an infection model for several clinically relevant fungal pathogens, such as C. albicans, C. glabrata, C. neoformans, and H. capsulatum (Mylonakis et al, 2002; Breger et al, 2007; Johnson et al, 2009), but with limited application in filamentous fungal pathogens like A. fumigatus
To further substantiate the ability of our C. elegans-A. fumigatus infection model to be employed in evaluating pathogenicity of A. fumigatus strains, clinical strain Af293, which is the parental strain of Af239-dsRed, was used for infection

Summary

Introduction

Aspergillus fumigatus is a saprophytic environmental fungus with ubiquitous airborne spores. It is an opportunistic fungal pathogen responsible for mycoses including invasive aspergillosis (IA) mostly in immunocompromised patients (Van De Veerdonk et al, 2017; Fang and Latge, 2018). Cases of aspergillosis have been reported in immunocompetent patients (Stevens and Melikian, 2011). Caenorhabditis elegans-Aspergillus fumigatus Infection Model resistant strains to the wide range of currently available drugs has posed a serious challenge as cases are rising globally (Prigitano et al, 2017, 2019; Abdolrasouli et al, 2018). With the limited repertoire of antifungal drug classes, there is the need to urgently discover new therapeutic option for this infection

Methods

Results

Conclusion