The Gene Is Required for the Growth and Virulence of the Human Pathogenic Fungus Aspergillus fumigatus.

Aspergillus fumigatus is an important opportunistic pathogenic fungus that causes invasive aspergillosis in immunocompromised humans. Regulated fungal growth is essential for disease development and progression. Thus, screening for genes that regulate fungal growth may lead to the identification of potential therapeutic targets for invasive aspergillosis (IA). Screening of the transfer DNA (T-DNA) random-insertion A. fumigatus mutants identified a severe growth deficiency mutant AFM2954 and featured as the mutated gene described as a putative intracellular protein transporter of unknown function. The deletion of exhibited severe growth defects and significantly increased the nematode and mouse survival rates and decreased the fungal loads and histopathological damages in mouse lungs. Transcriptomic analyses revealed expression changes associated with the cell wall synthesis, the tricarboxylic acid cycle (TCA cycle), and oxidative phosphorylation genes in the mutant. Deletion of the gene resulted in resistance to cell wall-perturbing agents and thickened cell wall as well as reduced ATP contents and mitochondrial membrane potential, suggested that affected the cell wall synthesis and mitochondrial function of A. fumigatus. All together, our study uncovered novel functions of in growth and virulence of A. fumigatus and provided a theoretical basis for the development of new therapeutic target for treating IA patients. Aspergillus fumigatus is the main causative agent of invasive aspergillosis in immunocompromised hosts, with up to 90% lethality. Nevertheless, the fungal factors that regulate the pathogenesis of A. fumigatus remain largely unknown. Better understanding of the mechanisms controlling growth of A. fumigatus may provide novel therapeutic targets. In the present study, we characterized in the opportunistic pathogen A. fumigatus. The function of remains unknown. We proved its important role in growth and virulence, likely because of its effects on cell wall synthesis and mitochondrial functions.