The C-22 sterol desaturase Erg5 is responsible for ergosterol biosynthesis and conidiation in Aspergillus fumigatus

Aspergillus fumigatus is the most prevalent saprophytic fungi and can cause severe invasive aspergillosis in immunocompromised individuals. For infection of A. fumigatus, the small hydrophobic conidia have been shown to play a dominant role. In this study, we found that deletion of erg5, a C-22 sterol desaturase gene which function in the last two steps of ergosterol biosynthesis, was sufficient to block ergosterol biosynthesis and conidiation. The deletion phenotype was further verified by a conditional expression strain of erg5 using the inducible tet-on system. Strikingly, erg5 mutant displays increased susceptibility to antifungal azoles itraconazole. RNA sequencing analysis showed that erg5 deficiency resulted in changes in transcription mainly related to lipid, carbohydrate, and amino acid metabolism. Genes encoding ergosterol biosynthesis-related enzymes were found to be up-regulated in erg5 null mutants. However, genes involved in asexual development, including upstream regulators, melanin biosynthesis enzymes, heterotrimeric G proteins, and MAPK signaling, were down-regulated to various degrees. Furthermore, metabolomic study revealed that erg5 deficiency also resulted in altered lipid and amino acid metabolism, which was consistent with our transcriptomics analysis. Collectively, our study established a link between ergosterol biosynthesis and asexual development at the transcriptomics and metabolomics level in A. fumigatus.