Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>

ABSTRACT The pathogenic fungus Aspergillus fumigatus is able to adapt to extremely variable environmental conditions. The A. fumigatus genome contains four genes coding for mitogen-activated protein kinases (MAPKs), which are important regulatory knots involved in diverse cellular responses. From a...

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Autores principales:	Adriana Oliveira Manfiolli, Filipe Silva Siqueira, Thaila Fernanda dos Reis, Patrick Van Dijck, Sanne Schrevens, Sandra Hoefgen, Martin Föge, Maria Straßburger, Leandro José de Assis, Thorsten Heinekamp, Marina Campos Rocha, Slavica Janevska, Axel A. Brakhage, Iran Malavazi, Gustavo H. Goldman, Vito Valiante
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Aspergillus fumigatus GPCR MAP kinases melanin Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2a88a6e1f3f546b38da33b11a7706562
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spelling	oai:doaj.org-article:2a88a6e1f3f546b38da33b11a77065622021-11-15T15:55:25ZMitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>10.1128/mBio.00215-192150-7511https://doaj.org/article/2a88a6e1f3f546b38da33b11a77065622019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00215-19https://doaj.org/toc/2150-7511ABSTRACT The pathogenic fungus Aspergillus fumigatus is able to adapt to extremely variable environmental conditions. The A. fumigatus genome contains four genes coding for mitogen-activated protein kinases (MAPKs), which are important regulatory knots involved in diverse cellular responses. From a clinical perspective, MAPK activity has been connected to salvage pathways, which can determine the failure of effective treatment of invasive mycoses using antifungal drugs. Here, we report the characterization of the Saccharomyces cerevisiae Fus3 ortholog in A. fumigatus, designated MpkB. We demonstrate that MpkB is important for conidiation and that its deletion induces a copious increase of dihydroxynaphthalene (DHN)-melanin production. Simultaneous deletion of mpkB and mpkA, the latter related to maintenance of the cell wall integrity, normalized DHN-melanin production. Localization studies revealed that MpkB translocates into the nuclei when A. fumigatus germlings are exposed to caspofungin stress, and this is dependent on the cross-talk interaction with MpkA. Additionally, DHN-melanin formation was also increased after deletion of genes coding for the Gα protein GpaA and for the G protein-coupled receptor GprM. Yeast two-hybrid and coimmunoprecipitation assays confirmed that GpaA and GprM interact, suggesting their role in the MpkB signaling cascade. IMPORTANCE Aspergillus fumigatus is the most important airborne human pathogenic fungus, causing thousands of deaths per year. Its lethality is due to late and often inaccurate diagnosis and the lack of efficient therapeutics. The failure of efficient prophylaxis and therapy is based on the ability of this pathogen to activate numerous salvage pathways that are capable of overcoming the different drug-derived stresses. A major role in the protection of A. fumigatus is played by melanins. Melanins are cell wall-associated macromolecules classified as virulence determinants. The understanding of the various signaling pathways acting in this organism can be used to elucidate the mechanism beyond melanin production and help to identify ideal drug targets.Adriana Oliveira ManfiolliFilipe Silva SiqueiraThaila Fernanda dos ReisPatrick Van DijckSanne SchrevensSandra HoefgenMartin FögeMaria StraßburgerLeandro José de AssisThorsten HeinekampMarina Campos RochaSlavica JanevskaAxel A. BrakhageIran MalavaziGustavo H. GoldmanVito ValianteAmerican Society for MicrobiologyarticleAspergillus fumigatusGPCRMAP kinasesmelaninMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus fumigatus GPCR MAP kinases melanin Microbiology QR1-502
spellingShingle	Aspergillus fumigatus GPCR MAP kinases melanin Microbiology QR1-502 Adriana Oliveira Manfiolli Filipe Silva Siqueira Thaila Fernanda dos Reis Patrick Van Dijck Sanne Schrevens Sandra Hoefgen Martin Föge Maria Straßburger Leandro José de Assis Thorsten Heinekamp Marina Campos Rocha Slavica Janevska Axel A. Brakhage Iran Malavazi Gustavo H. Goldman Vito Valiante Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
description	ABSTRACT The pathogenic fungus Aspergillus fumigatus is able to adapt to extremely variable environmental conditions. The A. fumigatus genome contains four genes coding for mitogen-activated protein kinases (MAPKs), which are important regulatory knots involved in diverse cellular responses. From a clinical perspective, MAPK activity has been connected to salvage pathways, which can determine the failure of effective treatment of invasive mycoses using antifungal drugs. Here, we report the characterization of the Saccharomyces cerevisiae Fus3 ortholog in A. fumigatus, designated MpkB. We demonstrate that MpkB is important for conidiation and that its deletion induces a copious increase of dihydroxynaphthalene (DHN)-melanin production. Simultaneous deletion of mpkB and mpkA, the latter related to maintenance of the cell wall integrity, normalized DHN-melanin production. Localization studies revealed that MpkB translocates into the nuclei when A. fumigatus germlings are exposed to caspofungin stress, and this is dependent on the cross-talk interaction with MpkA. Additionally, DHN-melanin formation was also increased after deletion of genes coding for the Gα protein GpaA and for the G protein-coupled receptor GprM. Yeast two-hybrid and coimmunoprecipitation assays confirmed that GpaA and GprM interact, suggesting their role in the MpkB signaling cascade. IMPORTANCE Aspergillus fumigatus is the most important airborne human pathogenic fungus, causing thousands of deaths per year. Its lethality is due to late and often inaccurate diagnosis and the lack of efficient therapeutics. The failure of efficient prophylaxis and therapy is based on the ability of this pathogen to activate numerous salvage pathways that are capable of overcoming the different drug-derived stresses. A major role in the protection of A. fumigatus is played by melanins. Melanins are cell wall-associated macromolecules classified as virulence determinants. The understanding of the various signaling pathways acting in this organism can be used to elucidate the mechanism beyond melanin production and help to identify ideal drug targets.
format	article
author	Adriana Oliveira Manfiolli Filipe Silva Siqueira Thaila Fernanda dos Reis Patrick Van Dijck Sanne Schrevens Sandra Hoefgen Martin Föge Maria Straßburger Leandro José de Assis Thorsten Heinekamp Marina Campos Rocha Slavica Janevska Axel A. Brakhage Iran Malavazi Gustavo H. Goldman Vito Valiante
author_facet	Adriana Oliveira Manfiolli Filipe Silva Siqueira Thaila Fernanda dos Reis Patrick Van Dijck Sanne Schrevens Sandra Hoefgen Martin Föge Maria Straßburger Leandro José de Assis Thorsten Heinekamp Marina Campos Rocha Slavica Janevska Axel A. Brakhage Iran Malavazi Gustavo H. Goldman Vito Valiante
author_sort	Adriana Oliveira Manfiolli
title	Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
title_short	Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
title_full	Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
title_fullStr	Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
title_full_unstemmed	Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>
title_sort	mitogen-activated protein kinase cross-talk interaction modulates the production of melanins in <named-content content-type="genus-species">aspergillus fumigatus</named-content>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/2a88a6e1f3f546b38da33b11a7706562
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Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in <named-content content-type="genus-species">Aspergillus fumigatus</named-content>

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