Title |
The C-22 sterol desaturase Erg5 is responsible for ergosterol biosynthesis and conidiation in Aspergillus fumigatus |
Author |
Nanbiao Long1 and Guowei Zhong2* |
Address |
1College of Medical Technology, Shaoyang University, Shaoyang 422004, P. R. China, 2School of Public Health, Nanjing Medical University, Nanjing 211166, P. R. China |
Bibliography |
Journal of Microbiology, 60(6),620-626, 2022,
|
DOI |
10.1007/s12275-022-1564-7
|
Key Words |
Aspergillus fumigatus, ergosterol biosynthesis, conidiation,
transcriptomics, metabolomics |
Abstract |
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. |