title: Macrophage Interaction with Paracoccidioides brasiliensis Yeast Cells Modulates Fungal Metabolism and Generates a Response to Oxidative Stress.
abstract: Macrophages are key players during Paracoccidioides brasiliensis infection. However, the relative contribution of the fungal response to counteracting macrophage activity remains poorly understood. In this work, we evaluated the P. brasiliensis proteomic response to macrophage internalization. A total of 308 differentially expressed proteins were detected in P. brasiliensis during infection. The positively regulated proteins included those involved in alternative carbon metabolism, such as enzymes involved in gluconeogenesis, beta-oxidation of fatty acids and amino acids catabolism. The down-regulated proteins during P. brasiliensis internalization in macrophages included those related to glycolysis and protein synthesis. Proteins involved in the oxidative stress response in P. brasiliensis yeast cells were also up-regulated during macrophage infection, including superoxide dismutases (SOD), thioredoxins (THX) and cytochrome c peroxidase (CCP). Antisense knockdown mutants evaluated the importance of CCP during macrophage infection. The results suggested that CCP is involved in a complex system of protection against oxidative stress and that gene silencing of this component of the antioxidant system diminished the survival of P. brasiliensis in macrophages and in a murine model of infection.
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Juliana Alves
authors.initials: JA
authors.lastname: Parente-Rocha
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil; Departamento de Ciências Fisiológicas, Universidade Federal do Amazonas, Manaus, Amazonas, Brazil.
authors.forename: Ana Flávia Alves
authors.initials: AF
authors.lastname: Parente
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Lilian Cristiane
authors.initials: LC
authors.lastname: Baeza
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Sheyla Maria Rondon Caixeta
authors.initials: SM
authors.lastname: Bonfim
authors.affiliation: Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia; Grupo de Investigación MICROBA, Escuela de Microbiología, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Orville
authors.initials: O
authors.lastname: Hernandez
authors.affiliation: Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia; Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Juan G
authors.initials: JG
authors.lastname: McEwen
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Alexandre Melo
authors.initials: AM
authors.lastname: Bailão
authors.affiliation: Instituto de Ciências Biomédicas, Departamento de Microbiologia, Laboratório de Micologia, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Carlos Pelleschi
authors.initials: CP
authors.lastname: Taborda
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Clayton Luiz
authors.initials: CL
authors.lastname: Borges
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: Célia Maria de Almeida
authors.initials: CM
authors.lastname: Soares
mesh_terms: D000818:Animals; D002460:Cell Line; D003578:Cytochrome-c Peroxidase / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D018384:Oxidative Stress; D010228:Paracoccidioides / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D013879:Thioredoxins; D003578:Cytochrome-c Peroxidase; D013482:Superoxide Dismutase