Insights into Aspergillus fumigatus morphogenesis and pathogenesis through the putative lipid transporter ArvA

<i>Aspergillus fumigatus</i> is a challenging fungal pathogen in the clinic in part due to increasing azole drug resistance. In this study, we observe that loss of the <i>A. fumigatus</i> gene <i>arvA</i> results in increased azole susceptibility and significant <i>in vitro</i> morphological changes highlighted by hyper-swollen conidia that yield stunted and polarity deficient hyphae. Importantly, despite these severe <i>in vitro</i> morphological and growth abnormalities, <i>ΔarvA</i> surprisingly retains full pathogenicity and virulence in two immunologically distinct murine models of invasive pulmonary aspergillosis. These results challenge our understanding of the in-host environment and how it mediates fungal morphogenesis and pathogenesis. These results, consequently, not only enhances our understanding of the role of <i>arvA</i> in <i>A. fumigatus</i> morphogenesis and drug susceptibility, but further emphasizes the importance of <i>in vivo</i> animal models in fully evaluating potential antifungal drug targets.