PMID- 25841799 OWN - NLM STAT- MEDLINE DCOM- 20160208 LR - 20161020 IS - 1769-714X (Electronic) IS - 1286-4579 (Linking) VI - 17 IP - 8 DP - 2015 Aug TI - The response of Paracoccidioides spp. to nitrosative stress. PG - 575-85 LID - S1286-4579(15)00064-7 [pii] LID - 10.1016/j.micinf.2015.03.012 [doi] AB - 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. CI - Copyright (c) 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. FAU - Parente, Ana F A AU - Parente AF AD - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade Federal de Goias, Campus Samambaia, Instituto de Ciencias Biologicas II (ICB II), 2 masculine Andar, Sala 206, Goiania, Goias, 74690-900, Brazil; Departamento de Ciencias Fisiologicas, Universidade Federal do Amazonas, Av. General Rodrigo Octavio, 6200, Coroado I, Manaus, Amazonas, 69077-000, Brazil. FAU - Naves, Priscila E C AU - Naves PE AD - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade Federal de Goias, Campus Samambaia, Instituto de Ciencias Biologicas II (ICB II), 2 masculine Andar, Sala 206, Goiania, Goias, 74690-900, Brazil. FAU - Pigosso, Laurine L AU - Pigosso LL AD - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade Federal de Goias, Campus Samambaia, Instituto de Ciencias Biologicas II (ICB II), 2 masculine Andar, Sala 206, Goiania, Goias, 74690-900, Brazil. FAU - Casaletti, Luciana AU - Casaletti L AD - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade Federal de Goias, Campus Samambaia, Instituto de Ciencias Biologicas II (ICB II), 2 masculine Andar, Sala 206, Goiania, Goias, 74690-900, Brazil. FAU - McEwen, Juan G AU - McEwen JG AD - Unidad de Biologia Celular y Molecular, Corporacion para Investigaciones Biologicas (CIB), Medellin, Calle 62 No. 52-59, 51922, Colombia; Facultad de Medicina, Universidad de Antioquia, Medellin, Carrera 51 D No. 62-29, 050010, Colombia. FAU - Parente-Rocha, Juliana A AU - Parente-Rocha JA AD - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade Federal de Goias, Campus Samambaia, Instituto de Ciencias Biologicas II (ICB II), 2 masculine Andar, Sala 206, Goiania, Goias, 74690-900, Brazil. FAU - Soares, Celia M A AU - Soares CM AD - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade Federal de Goias, Campus Samambaia, Instituto de Ciencias Biologicas II (ICB II), 2 masculine Andar, Sala 206, Goiania, Goias, 74690-900, Brazil. Electronic address: cmasoares@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150402 PL - France TA - Microbes Infect JT - Microbes and infection JID - 100883508 RN - 0 (Fungal Proteins) RN - 0 (Reactive Nitrogen Species) SB - IM MH - Fungal Proteins/genetics MH - Humans MH - Nitrosation/immunology MH - Oxidative Stress/genetics/*physiology MH - Paracoccidioides/genetics/*physiology MH - Paracoccidioidomycosis/microbiology MH - Reactive Nitrogen Species/immunology/*metabolism OTO - NOTNLM OT - Cytochrome c peroxidase OT - Functional analysis OT - Paracoccidioides spp. OT - Proteomic OT - Reactive nitrogen species EDAT- 2015/04/07 06:00 MHDA- 2016/02/09 06:00 CRDT- 2015/04/06 06:00 PHST- 2015/01/07 00:00 [received] PHST- 2015/03/05 00:00 [revised] PHST- 2015/03/23 00:00 [accepted] PHST- 2015/04/06 06:00 [entrez] PHST- 2015/04/07 06:00 [pubmed] PHST- 2016/02/09 06:00 [medline] AID - S1286-4579(15)00064-7 [pii] AID - 10.1016/j.micinf.2015.03.012 [doi] PST - ppublish SO - Microbes Infect. 2015 Aug;17(8):575-85. doi: 10.1016/j.micinf.2015.03.012. Epub 2015 Apr 2.