Comparative proteomic analysis to study the involvement of the Tor pathway in the human-pathogenic fungus Aspergillus fumigatus

ABSTRACT: The Tor kinase is one of the major regulatory nodes in a eukaryotic cell and until now, little is known about this kinase in filamentous fungi. Here, we analysed the Tor kinase in Aspergillus fumigatus, which is the most important airborne fungal pathogen of humans and the main causative agent of invasive aspergillosis. Because deletion of the single tor gene of A. fumigatus was apparently lethal, we generated a conditional lethal tor mutant. This was achieved by fusing the tor gene with the inducible xylose promoter and replacing the endogenous tor gene by the inducible xylp-tor gene cassette. The generated transgenic strain opened up the possibility to activate or silence the tor gene under controlled conditions. Since we did not observe any effect of rapamycin on Tor of A. fumigatus, the generation of the inducible Tor gene was even more valuable for an in-depth analysis of the Tor kinase. By LC-MS/MS analyses of mycelial proteins we identified the regulatory network of Tor. Tor controls a variety of genes and proteins involved in nutrient sensing, stress response, cell cycle progression, protein biosynthesis and degradation. Tor is a major kinase responsible for protein import into the mitochondria, and consequently responsible for the correct function of most processes occurring into these organelles, e.g. respiration and ornithine metabolism. Regulation of iron acquisition by Tor was found to be independent of the HapX transcription factor.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Aspergillus Fumigatus Cea10

TISSUE(S): Hyphal Cell

SUBMITTER: Thomas Krueger  

LAB HEAD: Dr. Olaf Kniemeyer

PROVIDER: PXD001601 | Pride | 2022-02-28

REPOSITORIES: Pride