title: Phosphosite-specific regulation of the oxidative-stress response of Paracoccidioides brasiliensis: a shotgun phosphoproteomic analysis.
abstract: Paracoccidioides brasiliensis, a thermally dimorphic fungus, is the causative agent of paracoccidioidomycosis, a systemic mycosis that is widespread in Latin America. This fungus is a facultative intracellular pathogen able to survive and replicate inside non-activated macrophages. Therefore, the survival of P. brasiliensis inside the host depends on the ability to adapt to oxidative stress induced by immune cells, especially alveolar macrophages. For several years, reactive oxygen species (ROS) were only associated with pathological processes. Currently, a plethora of roles for ROS in cell signaling have emerged. We have previously reported that low ROS concentrations cause cell proliferation in the human pathogenic fungus P. brasiliensis. In the present report, we investigated the influence of phosphorylation events in that process. Using a mass spectrometry-based approach, we mapped 440 phosphorylation sites in 230 P. brasiliensis proteins and showed that phosphorylation at different sites determines fungal responses to oxidative stress, which are regulated by phosphatases and kinases activities. Furthermore, we present additional evidence for a functional two-component signal transduction system in P. brasiliensis. These findings will help us to understand the phosphorylation events involved in the oxidative stress response.
authors: Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors: Alison F A
authors: AF
authors: Chaves
authors: Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors: Daniele G
authors: DG
authors: Castilho
authors: Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors: Marina V
authors: MV
authors: Navarro
authors: Laboratory of Applied Toxinology, Center of Toxins, Immune-response and Cell Signaling, Instituto Butantan, São Paulo, SP, Brazil.
authors: Ana K
authors: AK
authors: Oliveira
authors: Laboratory of Applied Toxinology, Center of Toxins, Immune-response and Cell Signaling, Instituto Butantan, São Paulo, SP, Brazil.
authors: Solange M T
authors: SM
authors: Serrano
authors: Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors: Alexandre K
authors: AK
authors: Tashima
authors: Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo, São Paulo, SP, Brazil; Department of Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, SP, Brazil. Electronic address: batista@unifesp.br.
authors: Wagner L
authors: WL
authors: Batista
mesh_terms: D005656:Fungal Proteins / Q000032:analysis*; D015966:Gene Expression Regulation, Fungal; D054884:Host-Pathogen Interactions; D006801:Humans; D013058:Mass Spectrometry; D018384:Oxidative Stress; D010228:Paracoccidioides / Q000472:pathogenicity*; D010750:Phosphoproteins / Q000032:analysis*; D020543:Proteome / Q000032:analysis*; D015398:Signal Transduction
chemical_list: D005656:Fungal Proteins; D010750:Phosphoproteins; D020543:Proteome
keywords: Oxidative stress; Paracoccidioides brasiliensis; Phosphorylation; Post-translational modification