title: The response of Paracoccidioides spp. to nitrosative stress.
abstract: Paracoccidioidomycosis (PCM) is an endemic disease in Latin America caused by species belonging to the genus Paracoccidioides. During infection, immune cells present a variety of defense mechanisms against pathogens. One of these defensive strategies is the production and release of nitric oxide (NO) and S-nitroso thiols (e.g., S-nitrosoglutathione, GSNO), which produce reactive nitrogen species (RNS). This results in damage to DNA and membranes, inhibition of respiration and inactivation of cellular enzymes. In response to nitrosative stress, human pathogenic fungi possess defense mechanisms to prevent the adverse effects of NO, which helps them survive during initial contact with the host immune system. To understand how Paracoccidioides spp. respond to nitrosative stress, we conducted this study to identify genes and proteins that might contribute to this response. The results of proteomic analysis demonstrated that nitrosative stress induced a reduction in the expression of proteins related to the mitochondrial electron transport chain. This hypothesis was supported by the reduced mitochondrial activity observed in the presence of GSNO. Additionally, lipids and branched chain amino acid metabolism enzymes were altered. The role played by enzymes acting in oxidative stress in the RNS response was remarkable. This interface among enzymes acting in both stress responses was confirmed by using a RNA approach to silence the ccp gene in Paracoccidioides. It was observed that mutants with low expression of the ccp gene were more sensitive to nitrosative stress.
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Campus Samambaia, Instituto de Ciências Biológicas II (ICB II), 2º Andar, Sala 206, Goiânia, Goiás, 74690-900, Brazil; Departamento de Ciências Fisiológicas, Universidade Federal do Amazonas, Av. General Rodrigo Octávio, 6200, Coroado I, Manaus, Amazonas, 69077-000, Brazil.
authors.forename: Ana F A
authors.initials: AF
authors.lastname: Parente
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Campus Samambaia, Instituto de Ciências Biológicas II (ICB II), 2º Andar, Sala 206, Goiânia, Goiás, 74690-900, Brazil.
authors.forename: Priscila E C
authors.initials: PE
authors.lastname: Naves
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Campus Samambaia, Instituto de Ciências Biológicas II (ICB II), 2º Andar, Sala 206, Goiânia, Goiás, 74690-900, Brazil.
authors.forename: Laurine L
authors.initials: LL
authors.lastname: Pigosso
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Campus Samambaia, Instituto de Ciências Biológicas II (ICB II), 2º Andar, Sala 206, Goiânia, Goiás, 74690-900, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Casaletti
authors.affiliation: Unidad de Biología Celular y Molecular, Corporación para Investigaciones Biológicas (CIB), Medellín, Calle 62 No. 52-59, 51922, Colombia; Facultad de Medicina, Universidad de Antioquia, Medellín, Carrera 51 D No. 62-29, 050010, 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, Campus Samambaia, Instituto de Ciências Biológicas II (ICB II), 2º Andar, Sala 206, Goiânia, Goiás, 74690-900, Brazil.
authors.forename: Juliana A
authors.initials: JA
authors.lastname: Parente-Rocha
authors.affiliation: Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Campus Samambaia, Instituto de Ciências Biológicas II (ICB II), 2º Andar, Sala 206, Goiânia, Goiás, 74690-900, Brazil. Electronic address: cmasoares@gmail.com.
authors.forename: Célia M A
authors.initials: CM
authors.lastname: Soares
mesh_terms: D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D015538:Nitrosation / Q000276:immunology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D010228:Paracoccidioides / Q000235:genetics / Q000502:physiology*; D010229:Paracoccidioidomycosis / Q000382:microbiology; D026361:Reactive Nitrogen Species / Q000276:immunology / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D026361:Reactive Nitrogen Species
keywords: Cytochrome c peroxidase; Functional analysis; Paracoccidioides spp.; Proteomic; Reactive nitrogen species