title: Systematic Global Analysis of Genes Encoding Protein Phosphatases in Aspergillus fumigatus.
abstract: Aspergillus fumigatus is a fungal pathogen that causes several invasive and noninvasive diseases named aspergillosis. This disease is generally regarded as multifactorial, considering that several pathogenicity determinants are present during the establishment of this illness. It is necessary to obtain an increased knowledge of how, and which, A. fumigatus signal transduction pathways are engaged in the regulation of these processes. Protein phosphatases are essential to several signal transduction pathways. We identified 32 phosphatase catalytic subunit-encoding genes in A. fumigatus, of which we were able to construct 24 viable deletion mutants. The role of nine phosphatase mutants in the HOG (high osmolarity glycerol response) pathway was evaluated by measuring phosphorylation of the p38 MAPK (SakA) and expression of osmo-dependent genes. We were also able to identify 11 phosphatases involved in iron assimilation, six that are related to gliotoxin resistance, and three implicated in gliotoxin production. These results present the creation of a fundamental resource for the study of signaling in A. fumigatus and its implications in the regulation of pathogenicity determinants and virulence in this important pathogen.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 13083-970 Ribeirão Preto, Brazil.
authors.forename: Lizziane K
authors.initials: LK
authors.lastname: Winkelströter
authors.affiliation: Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Dolan
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 13083-970 Ribeirão Preto, Brazil.
authors.forename: Thaila
authors.initials: T
authors.lastname: Fernanda Dos Reis
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 13083-970 Ribeirão Preto, Brazil.
authors.forename: Vinícius Leite Pedro
authors.initials: VL
authors.lastname: Bom
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 13083-970 Ribeirão Preto, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Alves de Castro
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hagiwara
authors.affiliation: Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: Raneem
authors.initials: R
authors.lastname: Alowni
authors.affiliation: Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jones
authors.affiliation: Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: Doyle
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 13083-970 Ribeirão Preto, Brazil.
authors.forename: Neil Andrew
authors.initials: NA
authors.lastname: Brown
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 13083-970 Ribeirão Preto, Brazil National Laboratory of Science and Technology of Bioethanol (CTBE), 13083-970 Campinas, Brazil ggoldman@usp.br.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D001232:Aspergillus fumigatus / Q000201:enzymology*; D020134:Catalytic Domain; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D005656:Fungal Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005912:Gliotoxin / Q000032:analysis / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D010802:Phylogeny; D017262:Siderophores / Q000032:analysis; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry; D014774:Virulence / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D017262:Siderophores; D005912:Gliotoxin; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases
keywords: Aspergillus fumigatus; HOG phosphatases; gliotoxin; iron metabolism; protein phosphatases