Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection

Patrícia Alves de Castro; Camila Figueiredo Pinzan; Thaila Fernanda Dos Reis; Clara Valero; Norman Van Rhijn; Carla Menegatti; Ivan Lucas de Freitas Migliorini; Michael Bromley; Alastair B Fleming; Aimee M Traynor; Özlem Sarikaya-Bayram; Özgür Bayram; Iran Malavazi; Frank Ebel; Júlio César Jerônimo Barbosa; Taícia Fill; Monica Tallarico Pupo; Gustavo H Goldman

doi:10.1038/s41467-023-44329-1

Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection

Patrícia Alves de Castro, Camila Figueiredo Pinzan, Thaila Fernanda Dos Reis, Clara Valero, Norman Van Rhijn, Carla Menegatti, Ivan Lucas de Freitas Migliorini, Michael Bromley, Alastair B Fleming, Aimee M Traynor, Özlem Sarikaya-Bayram, Özgür Bayram, Iran Malavazi, Frank Ebel, Júlio César Jerônimo Barbosa, Taícia Fill, Monica Tallarico Pupo, Gustavo H Goldman

Research output: Contribution to journal › Article › peer-review

Abstract

Aspergillus fumigatus is a saprophytic fungus that can cause a variety of human diseases known as aspergillosis. Mycotoxin gliotoxin (GT) production is important for its virulence and must be tightly regulated to avoid excess production and toxicity to the fungus. GT self-protection by GliT oxidoreductase and GtmA methyltransferase activities is related to the subcellular localization of these enzymes and how GT can be sequestered from the cytoplasm to avoid increased cell damage. Here, we show that GliT:GFP and GtmA:GFP are localized in the cytoplasm and in vacuoles during GT production. The Mitogen-Activated Protein kinase MpkA is essential for GT production and self-protection, interacts physically with GliT and GtmA and it is necessary for their regulation and subsequent presence in the vacuoles. The sensor histidine kinase SlnA Sln1 is important for modulation of MpkA phosphorylation. Our work emphasizes the importance of MpkA and compartmentalization of cellular events for GT production and self-defense.

Original language	English
Article number	33
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-44329-1
Publication status	Published - 2 Jan 2024

Keywords

Humans
Aspergillus fumigatus/metabolism
Gliotoxin/metabolism
Fungal Proteins/genetics
Mitogen-Activated Protein Kinases/genetics
Aspergillosis/microbiology

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Alves de Castro, P., Figueiredo Pinzan, C., Dos Reis, T. F., Valero, C., Van Rhijn, N., Menegatti, C., de Freitas Migliorini, I. L., Bromley, M., Fleming, A. B., Traynor, A. M., Sarikaya-Bayram, Ö., Bayram, Ö., Malavazi, I., Ebel, F., Barbosa, J. C. J., Fill, T., Pupo, M. T., & Goldman, G. H. (2024). Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection. Nature Communications, 15(1), Article 33. https://doi.org/10.1038/s41467-023-44329-1

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title = "Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection",

abstract = "Aspergillus fumigatus is a saprophytic fungus that can cause a variety of human diseases known as aspergillosis. Mycotoxin gliotoxin (GT) production is important for its virulence and must be tightly regulated to avoid excess production and toxicity to the fungus. GT self-protection by GliT oxidoreductase and GtmA methyltransferase activities is related to the subcellular localization of these enzymes and how GT can be sequestered from the cytoplasm to avoid increased cell damage. Here, we show that GliT:GFP and GtmA:GFP are localized in the cytoplasm and in vacuoles during GT production. The Mitogen-Activated Protein kinase MpkA is essential for GT production and self-protection, interacts physically with GliT and GtmA and it is necessary for their regulation and subsequent presence in the vacuoles. The sensor histidine kinase SlnA Sln1 is important for modulation of MpkA phosphorylation. Our work emphasizes the importance of MpkA and compartmentalization of cellular events for GT production and self-defense. ",

keywords = "Humans, Aspergillus fumigatus/metabolism, Gliotoxin/metabolism, Fungal Proteins/genetics, Mitogen-Activated Protein Kinases/genetics, Aspergillosis/microbiology",

author = "{Alves de Castro}, Patr{\'i}cia and {Figueiredo Pinzan}, Camila and {Dos Reis}, {Thaila Fernanda} and Clara Valero and {Van Rhijn}, Norman and Carla Menegatti and {de Freitas Migliorini}, {Ivan Lucas} and Michael Bromley and Fleming, {Alastair B} and Traynor, {Aimee M} and {\"O}zlem Sarikaya-Bayram and {\"O}zg{\"u}r Bayram and Iran Malavazi and Frank Ebel and Barbosa, {J{\'u}lio C{\'e}sar Jer{\^o}nimo} and Ta{\'i}cia Fill and Pupo, {Monica Tallarico} and Goldman, {Gustavo H}",

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doi = "10.1038/s41467-023-44329-1",

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journal = "Nature Communications",

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Alves de Castro, P, Figueiredo Pinzan, C, Dos Reis, TF, Valero, C, Van Rhijn, N, Menegatti, C, de Freitas Migliorini, IL, Bromley, M, Fleming, AB, Traynor, AM, Sarikaya-Bayram, Ö, Bayram, Ö, Malavazi, I, Ebel, F, Barbosa, JCJ, Fill, T, Pupo, MT & Goldman, GH 2024, 'Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection', Nature Communications, vol. 15, no. 1, 33. https://doi.org/10.1038/s41467-023-44329-1

TY - JOUR

T1 - Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection

AU - Alves de Castro, Patrícia

AU - Figueiredo Pinzan, Camila

AU - Dos Reis, Thaila Fernanda

AU - Valero, Clara

AU - Van Rhijn, Norman

AU - Menegatti, Carla

AU - de Freitas Migliorini, Ivan Lucas

AU - Bromley, Michael

AU - Fleming, Alastair B

AU - Traynor, Aimee M

AU - Sarikaya-Bayram, Özlem

AU - Bayram, Özgür

AU - Malavazi, Iran

AU - Ebel, Frank

AU - Barbosa, Júlio César Jerônimo

AU - Fill, Taícia

AU - Pupo, Monica Tallarico

AU - Goldman, Gustavo H

PY - 2024/1/2

Y1 - 2024/1/2

N2 - Aspergillus fumigatus is a saprophytic fungus that can cause a variety of human diseases known as aspergillosis. Mycotoxin gliotoxin (GT) production is important for its virulence and must be tightly regulated to avoid excess production and toxicity to the fungus. GT self-protection by GliT oxidoreductase and GtmA methyltransferase activities is related to the subcellular localization of these enzymes and how GT can be sequestered from the cytoplasm to avoid increased cell damage. Here, we show that GliT:GFP and GtmA:GFP are localized in the cytoplasm and in vacuoles during GT production. The Mitogen-Activated Protein kinase MpkA is essential for GT production and self-protection, interacts physically with GliT and GtmA and it is necessary for their regulation and subsequent presence in the vacuoles. The sensor histidine kinase SlnA Sln1 is important for modulation of MpkA phosphorylation. Our work emphasizes the importance of MpkA and compartmentalization of cellular events for GT production and self-defense.

AB - Aspergillus fumigatus is a saprophytic fungus that can cause a variety of human diseases known as aspergillosis. Mycotoxin gliotoxin (GT) production is important for its virulence and must be tightly regulated to avoid excess production and toxicity to the fungus. GT self-protection by GliT oxidoreductase and GtmA methyltransferase activities is related to the subcellular localization of these enzymes and how GT can be sequestered from the cytoplasm to avoid increased cell damage. Here, we show that GliT:GFP and GtmA:GFP are localized in the cytoplasm and in vacuoles during GT production. The Mitogen-Activated Protein kinase MpkA is essential for GT production and self-protection, interacts physically with GliT and GtmA and it is necessary for their regulation and subsequent presence in the vacuoles. The sensor histidine kinase SlnA Sln1 is important for modulation of MpkA phosphorylation. Our work emphasizes the importance of MpkA and compartmentalization of cellular events for GT production and self-defense.

KW - Humans

KW - Aspergillus fumigatus/metabolism

KW - Gliotoxin/metabolism

KW - Fungal Proteins/genetics

KW - Mitogen-Activated Protein Kinases/genetics

KW - Aspergillosis/microbiology

UR - http://www.scopus.com/inward/record.url?scp=85181256583&partnerID=8YFLogxK

U2 - 10.1038/s41467-023-44329-1

DO - 10.1038/s41467-023-44329-1

M3 - Article

C2 - 38167253

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 33

ER -

Aspergillus fumigatus mitogen-activated protein kinase MpkA is involved in gliotoxin production and self-protection

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