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 Pacheco Fill, Mônica Tallarico Pupo, Gustavo H. Goldman
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 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.