title: Identification of Scedosporium boydii catalase A1 gene, a reactive oxygen species detoxification factor highly expressed in response to oxidative stress and phagocytic cells.
abstract: Scedosporium boydii is an opportunistic filamentous fungus which may be responsible for a large variety of infections in both immunocompetent and immunocompromised individuals. This fungus belongs to the Scedosporium apiospermum species complex which usually ranks second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). Species of the S. apiospermum complex are able to chronically colonize the CF airways suggesting pathogenic mechanisms allowing persistence and growth of these fungi in the respiratory tract. Few putative virulence factors have been purified and characterized so far in the S. apiospermum complex including a cytosolic Cu,Zn-superoxide dismutase (SOD) and a monofunctional catalase (catalase A1). Upon microbial infection, host phagocytes release reactive oxygen species (ROS), such as hydrogen peroxide, as part of the antimicrobial response. Catalases are known to protect pathogens against ROS by degradation of the hydrogen peroxide. Here, we identified the S. boydii catalase A1 gene (CATA1) and investigated its expression in response to the environmental conditions encountered in the CF airways and to the oxidative stress. Results showed that S. boydii CATA1 gene expression is not affected by hypoxia, hypercapnia or pH changes. In contrast, CATA1 gene was overexpressed in response to a chemically induced oxidative stress with a relative gene expression 37-fold higher in the presence of 250 μM H(2)O(2), 20-fold higher with 250 μM menadione and 5-fold higher with 2 mM paraquat. Moreover, S. boydii CATA1 gene expression progressively increased upon exposure to activated THP-1-derived macrophages, reaching a maximum after 12 h (26 fold). Activated HL60-derived neutrophils and activated human peripheral blood neutrophils more rapidly induced S. boydii CATA1 gene overexpression, a maximum gene expression level being reached at 75 min (17 fold) and 60 min (15 fold), respectively. In contrast expression of the gene encoding the Cu,Zn-SOD (SODC gene) was not affected by H(2)O(2), menadione, paraquat or in co-culture with phagocytic cells. These results suggest that S. boydii CATA1 gene is highly stimulated by the oxidative burst response whereas SODC gene is constitutively expressed.
authors.affiliation: L'UNAM Université, Université d'Angers, Groupe d'Etude des Interactions Hôte-Pathogène, UPRES EA 3142, Angers, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Mina
authors.affiliation: L'UNAM Université, Université d'Angers, Groupe d'Etude des Interactions Hôte-Pathogène, UPRES EA 3142, Angers, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Staerck
authors.affiliation: L'UNAM Université, Université d'Angers, Immunité Innée et Immunothérapie, Angers, France; Inserm UMR 892, Angers, France; CNRS UMR 6299, Angers, France.
authors.forename: Sènan M
authors.initials: SM
authors.lastname: d'Almeida
authors.affiliation: L'UNAM Université, Université d'Angers, Groupe d'Etude des Interactions Hôte-Pathogène, UPRES EA 3142, Angers, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Marot
authors.affiliation: L'UNAM Université, Université d'Angers, Immunité Innée et Immunothérapie, Angers, France; Inserm UMR 892, Angers, France; CNRS UMR 6299, Angers, France; Laboratoire d'Immunologie et Allergologie, Centre Hospitalier Universitaire d'Angers, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
authors.affiliation: L'UNAM Université, Université d'Angers, Groupe d'Etude des Interactions Hôte-Pathogène, UPRES EA 3142, Angers, France.
authors.forename: Alphonse
authors.initials: A
authors.lastname: Calenda
authors.affiliation: L'UNAM Université, Université d'Angers, Immunité Innée et Immunothérapie, Angers, France; Inserm UMR 892, Angers, France; CNRS UMR 6299, Angers, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Tabiasco
authors.affiliation: L'UNAM Université, Université d'Angers, Groupe d'Etude des Interactions Hôte-Pathogène, UPRES EA 3142, Angers, France; Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Universitaire d'Angers, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Bouchara
authors.affiliation: L'UNAM Université, Université d'Angers, Groupe d'Etude des Interactions Hôte-Pathogène, UPRES EA 3142, Angers, France. Electronic address: maxime.fleury@univ-angers.fr.
authors.forename: Maxime J J
authors.initials: MJJ
authors.lastname: Fleury
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism / Q000382:microbiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008969:Molecular Sequence Data; D009181:Mycoses / Q000378:metabolism / Q000382:microbiology*; D018384:Oxidative Stress; D010586:Phagocytes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D021681:Scedosporium / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase
keywords: Catalase; Cystic fibrosis; Phagocytes; ROS; SOD; Scedosporium apiospermum complex