Frawley, Dean and Stroe, Maria C. and Oakley, Berl and Heinekamp, Thorsten and Straßburger, Maria and Fleming, Alastair B. and Brakhage, Axel A. and Bayram, Ozgur (2020) The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus. Frontiers in Microbiology, 11 (811). ISSN 1664-302X

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Abstract

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.

Item Type:	Article
Additional Information:	Published under the Creative Commons Attribution licence (CC-BY). Cite as: Frawley D, Stroe MC, Oakley BR, Heinekamp T, Straßburger M, Fleming AB, Brakhage AA and Bayram Ö (2020) The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus. Front. Microbiol. 11:811. doi: 10.3389/fmicb.2020.00811 Fudning: This study was funded by a Maynooth University John and Pat Hume Scholarship and an IRC postgraduate scholarship (GOIPG/2018/35) to DF and a Science Foundation Ireland grant (Grant No: 13/CDA/2142) to ÖB. MS facility in Maynooth University was funded by SFI Grant No: 12/RI/2346(3). MS and AB were funded by the Federal Ministry of Education and Research (BMBF, grant number 03ZZ0803A).
Keywords:	Aspergillus fumigatus; gliotoxin; pheromone module; secondary metabolism; MAP Kinases; stress responses; asexual sporulation;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	13533
Identification Number:	https://doi.org/10.3389/fmicb.2020.00811
Depositing User:	Ozgur Bayram
Date Deposited:	05 Nov 2020 16:43
Journal or Publication Title:	Frontiers in Microbiology
Publisher:	Frontiers
Refereed:	Yes
Funders:	John and Pat Hume Scholarship, Irish Research Council (IRC), Science Foundation Ireland (SFI), Federal Ministry of Education and Research (BMBF)
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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