title: The mitogen-activated protein kinase MpkA of Aspergillus fumigatus regulates cell wall signaling and oxidative stress response.
abstract: Mitogen-activated protein kinase (MAPK) signaling pathways are involved in the regulation of various cellular responses in eukaryotes. In fungal pathogens they are of special interest because of their possible contribution to pathogenicity. Bioinformatic analysis of the genome of the most prevalent airborne human pathogenic fungus Aspergillus fumigatus, revealed the presence of four distinct MAPK-encoding genes. Here, we present the detailed functional analysis of one of these MAPKs, MpkA. Comparative analysis revealed similarities of MpkA with MAPKs involved in cell wall integrity signaling of other fungi. Accordingly, the analysis of mpkA deletion mutants revealed severe sensitivity of the mutants against cell wall active compounds, drastical alterations of the fungal morphology and increased resistance against oxidative stress. The expression of mpkA was induced by cell wall damaging conditions. Despite its involvement in cell wall signaling no influence on virulence of the deletion of mpkA was observed in a murine infection model.
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Beutenbergstrasse 11a, 07745 Jena, Germany.
authors.forename: Vito
authors.initials: V
authors.lastname: Valiante
authors.forename: Thorsten
authors.initials: T
authors.lastname: Heinekamp
authors.forename: Radhika
authors.initials: R
authors.lastname: Jain
authors.forename: Albert
authors.initials: A
authors.lastname: Härtl
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D019677:Artificial Gene Fusion; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D001557:Benzenesulfonates / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002473:Cell Wall / Q000187:drug effects; D003224:Congo Red / Q000494:pharmacology; D003958:Diamide / Q000494:pharmacology; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D017930:Genes, Reporter; D005816:Genetic Complementation Test; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D015398:Signal Transduction; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D016019:Survival Analysis; D014774:Virulence; D024483:Vitamin K 3 / Q000494:pharmacology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D001557:Benzenesulfonates; D016877:Oxidants; D003958:Diamide; D012967:Sodium Dodecyl Sulfate; D002110:Caffeine; D003224:Congo Red; D024483:Vitamin K 3; C007061:C.I. Fluorescent Brightening Agent 28; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D001616:beta-Galactosidase