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

Patrícia Alves de Castro, Camila Figueiredo Pinzan, Thaila Fernanda Reis, Clara Valero, Norman Rhijn, Carla Menegatti, Ivan Lucas 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 and Gustavo H. Goldman ()
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Patrícia Alves de Castro: Universidade de São Paulo
Camila Figueiredo Pinzan: Universidade de São Paulo
Thaila Fernanda Reis: Universidade de São Paulo
Clara Valero: Universidade de São Paulo
Norman Rhijn: University of Manchester
Carla Menegatti: Universidade de São Paulo
Ivan Lucas Freitas Migliorini: Universidade de São Paulo
Michael Bromley: University of Manchester
Alastair B. Fleming: Trinity College Dublin
Aimee M. Traynor: Maynooth University
Özlem Sarikaya-Bayram: Maynooth University
Özgür Bayram: Maynooth University
Iran Malavazi: Universidade Federal de São Carlos
Frank Ebel: Medizinische Fakultät, LMU
Júlio César Jerônimo Barbosa: Universidade Estadual de Campinas
Taícia Fill: Universidade Estadual de Campinas
Monica Tallarico Pupo: Universidade de São Paulo
Gustavo H. Goldman: Universidade de São Paulo

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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 SlnASln1 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.

Date: 2024
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DOI: 10.1038/s41467-023-44329-1

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