The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus
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 t...
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.00811/full |
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| author | Dean Frawley Maria C. Stroe Berl R. Oakley Thorsten Heinekamp Maria Straßburger Alastair B. Fleming Axel A. Brakhage Axel A. Brakhage Özgür Bayram |
| author_facet | Dean Frawley Maria C. Stroe Berl R. Oakley Thorsten Heinekamp Maria Straßburger Alastair B. Fleming Axel A. Brakhage Axel A. Brakhage Özgür Bayram |
| author_sort | Dean Frawley |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T14:53:58Z |
| format | Article |
| id | doaj.art-798e6968524144d2a4aea6fe601bc40c |
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| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-13T14:53:58Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-798e6968524144d2a4aea6fe601bc40c2022-12-21T23:41:17ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-05-011110.3389/fmicb.2020.00811538432The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatusDean Frawley0Maria C. Stroe1Berl R. Oakley2Thorsten Heinekamp3Maria Straßburger4Alastair B. Fleming5Axel A. Brakhage6Axel A. Brakhage7Özgür Bayram8Department of Biology, Fungal Genetics and Secondary Metabolism Laboratory, Maynooth University, Maynooth, IrelandDepartment of Molecular and Applied Microbiology, Hans Knöll Institute (HKI), Leibniz Institute for Natural Product Research and Infection Biology, Jena, GermanyDepartment of Molecular Biosciences, University of Kansas, Lawrence, KS, United StatesDepartment of Molecular and Applied Microbiology, Hans Knöll Institute (HKI), Leibniz Institute for Natural Product Research and Infection Biology, Jena, GermanyTransfer Group Antiinfectives, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, GermanyDepartment of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin, IrelandDepartment of Molecular and Applied Microbiology, Hans Knöll Institute (HKI), Leibniz Institute for Natural Product Research and Infection Biology, Jena, GermanyDepartment of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University, Jena, GermanyDepartment of Biology, Fungal Genetics and Secondary Metabolism Laboratory, Maynooth University, Maynooth, IrelandIn 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.https://www.frontiersin.org/article/10.3389/fmicb.2020.00811/fullAspergillus fumigatusgliotoxinpheromone modulesecondary metabolismMAP Kinasesstress responses |
| spellingShingle | Dean Frawley Maria C. Stroe Berl R. Oakley Thorsten Heinekamp Maria Straßburger Alastair B. Fleming Axel A. Brakhage Axel A. Brakhage Özgür Bayram The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus Frontiers in Microbiology Aspergillus fumigatus gliotoxin pheromone module secondary metabolism MAP Kinases stress responses |
| title | The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus |
| title_full | The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus |
| title_fullStr | The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus |
| title_full_unstemmed | The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus |
| title_short | The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus |
| title_sort | pheromone module stec mkkb mpkb sted hame regulates development stress responses and secondary metabolism in aspergillus fumigatus |
| topic | Aspergillus fumigatus gliotoxin pheromone module secondary metabolism MAP Kinases stress responses |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.00811/full |
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