TheAspergillus fumigatus maiAgene contributes to cell wall homeostasis and fungal virulence

Abstract

AbstractIn this study, two distinctin vitroinfection models ofAspergillus fumigatus, using murine macrophages (RAW264.7) and human lung epithelial cells (A549), were employed to identify the genes important for fungal adaptation during infection. Transcriptomic analyses of co-incubatedAspergillusuncovered 140 fungal genes up-regulated in common between both models that, when compared with a previously publishedin vivotranscriptomic study, allowed the identification of 13 genes consistently up-regulated in all three infection conditions. Among them, themaiAgene, responsible for a critical step in the L-phenylalanine degradation pathway, was identified. Disruption ofmaiAresulted in a mutant strain unable to complete the Phe degradation pathway, leading to an excessive production of pyomelanin when this amino acid served as the sole carbon source. Moreover, the disruption mutant exhibited noticeable cell wall abnormalities, with reduced levels of β-glucans within the cell wall. themaiA-1mutant strain induced reduced inflammation in primary macrophages and displayed significantly lower virulence in a neutropenic mouse model of infection. This is the first study linking theA. fumigatus maiAgene to fungal cell wall homeostasis and virulence.