title: High osmolarity glycerol response PtcB phosphatase is important for Aspergillus fumigatus virulence.
abstract: Aspergillus fumigatus is a fungal pathogen that is capable of adapting to different host niches and to avoid host defenses. An enhanced understanding of how, and which, A. fumigatus signal transduction pathways are engaged in the regulation of these processes is essential for the development of improved disease control strategies. Protein phosphatases are central to numerous signal transduction pathways. To comprehend the functions of protein phosphatases in A. fumigatus, 32 phosphatase catalytic subunit encoding genes were identified. We have recognized PtcB as one of the phosphatases involved in the high osmolarity glycerol response (HOG) pathway. The ΔptcB mutant has both increased phosphorylation of the p38 MAPK (SakA) and expression of osmo-dependent genes. The ΔptcB strain was more sensitive to cell wall damaging agents, had increased chitin and β-1,3-glucan, and impaired biofilm formation. The ΔptcB strain was avirulent in a murine model of invasive pulmonary aspergillosis. These results stress the importance of the HOG pathway in the regulation of pathogenicity determinants and virulence in A. fumigatus.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Lizziane K
authors.initials: LK
authors.lastname: Winkelströter
authors.forename: Vinícius Leite Pedro
authors.initials: VL
authors.lastname: Bom
authors.forename: Patrícia Alves
authors.initials: PA
authors.lastname: de Castro
authors.forename: Leandra Naira Zambelli
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Maria Helena S
authors.initials: MH
authors.lastname: Goldman
authors.forename: Neil Andrew
authors.initials: NA
authors.lastname: Brown
authors.forename: Ranjith
authors.initials: R
authors.lastname: Rajendran
authors.forename: Gordon
authors.initials: G
authors.lastname: Ramage
authors.forename: Elodie
authors.initials: E
authors.lastname: Bovier
authors.forename: Thaila Fernanda
authors.initials: TF
authors.lastname: Dos Reis
authors.forename: Marcela
authors.initials: M
authors.lastname: Savoldi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hagiwara
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology* / Q000648:ultrastructure; D018441:Biofilms / Q000254:growth & development; D002473:Cell Wall / Q000378:metabolism; D002686:Chitin / Q000378:metabolism; D019295:Computational Biology; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005990:Glycerol / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009994:Osmolar Concentration; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D047071:beta-Glucans / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D047071:beta-Glucans; D002686:Chitin; C033363:beta-1,3-glucan; D010744:Phosphoric Monoester Hydrolases; D005990:Glycerol