The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus .

Autor: Frawley D; Department of Biology, Fungal Genetics and Secondary Metabolism Laboratory, Maynooth University, Maynooth, Ireland., Stroe MC; Department of Molecular and Applied Microbiology, Hans Knöll Institute (HKI), Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany., Oakley BR; Department of Molecular Biosciences, University of Kansas, Lawrence, KS, United States., Heinekamp T; Department of Molecular and Applied Microbiology, Hans Knöll Institute (HKI), Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany., Straßburger M; Transfer Group Antiinfectives, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany., Fleming AB; Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin, Ireland., Brakhage AA; Department of Molecular and Applied Microbiology, Hans Knöll Institute (HKI), Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany.; Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University, Jena, Germany., Bayram Ö; Department of Biology, Fungal Genetics and Secondary Metabolism Laboratory, Maynooth University, Maynooth, Ireland.
Jazyk: angličtina
Zdroj: Frontiers in microbiology [Front Microbiol] 2020 May 07; Vol. 11, pp. 811. Date of Electronic Publication: 2020 May 07 (Print Publication: 2020).
DOI: 10.3389/fmicb.2020.00811
Abstrakt: In order for eukaryotes to efficiently detect and respond to environmental stimuli, a myriad of protein signaling pathways are utilized. An example of highly conserved signaling pathways in eukaryotes are the mitogen-activated protein kinase (MAPK) pathways. In fungi, MAPK pathways have been shown to regulate a diverse array of biological processes, such as asexual and sexual development, stress responses and the production of secondary metabolites (SMs). In the model fungus Aspergillus nidulans , a MAPK pathway known as the pheromone module is utilized to regulate both development and SM production. This signaling cascade consists of the three kinases SteC, MkkB, and MpkB, as well as the SteD adaptor protein and the HamE scaffold. In this study, homologs of each of these proteins have been identified in the opportunistic human pathogen A. fumigatus. By performing epitope tagging and mass spectrometry experiments, we have shown that these proteins form a pentameric complex, similar to what is observed in A. nidulans. This complex has been shown to assemble in the cytoplasm and MpkB enters the nucleus, where it would presumably interact with various transcription factors. Pheromone module mutant strains exhibit drastic reductions in asexual sporulation, vegetative growth rate and production of SMs, such as gliotoxin. Mutants also display increased sensitivity to cell wall and oxidative stress agents. Overall, these data provide evidence of the existence of a conserved MAP kinase signaling pathway in Aspergillus species and suggest that this pathway is critical for the regulation of fungal development and secondary metabolism.
(Copyright © 2020 Frawley, Stroe, Oakley, Heinekamp, Straßburger, Fleming, Brakhage and Bayram.)
Databáze: MEDLINE