Phosphosite-specific regulation of the oxidative-stress response of Paracoccidioides brasiliensis: a shotgun phosphoproteomic analysis

Author(s)

Chaves, Alison F. A. ^[1] ; Castilho, Daniele G. ^[1] ; Navarro, Marina V. ^[1] ; Oliveira, Ana K. ; Serrano, Solange M. T. ^[2] ; Tashima, Alexandre K. ; Batista, Wagner L.

Affiliation

^[1] Inst Butantan, Ctr Toxins, Lab Appl Toxinol, Immune Response & Cell Signaling, Sao Paulo, SP, Brazil. Tashima, Alexandre K., Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP, Brazil. Batista, Wagner L., Univ Fed Sao Paulo, Dept Pharmaceut Sci, Diadema, SP - Brazil

^[2] Batista, Wagner L., Univ Fed Sao Paulo, Dept Microbiol Immunol \& Parasitol, Sao Paulo, SP, Brazil. Oliveira, Ana K., Inst Butantan, Ctr Toxins, Lab Appl Toxinol, Immune Response & Cell Signaling, Sao Paulo, SP, Brazil. Tashima, Alexandre K., Univ Fed Sao - Brazil

• Document type: Journal article
• Source: Microbes and Infection; v. 19, n. 1, p. 34-46, JAN 2017.
• Web of Science Citations: 3

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. (C) 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. (AU)

• FAPESP's process: 14/13961-1 - Role of secreted aspartyl protease (PbSAP) in virulence and dimorphism in the pathogenic fungus Paracoccidioides brasiliensis
• Grantee: Wagner Luiz Batista
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/14392-2 - Evaluation of the involvement of Ras GTPase from Paracoccidioides brasiliensis in thermo-dimorphism and during oxidative and nitrosative stress
• Grantee: Wagner Luiz Batista
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/19321-9 - Proteomic and peptidomic characterization of Brazilian spider venoms by mass spectrometry
• Grantee: Alexandre Keiji Tashima
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/17530-0 - Evaluation of Paracoccidioides brasiliensis phosphoproteome under oxidative stress
• Grantee: Alison Felipe Alencar Chaves
• Support Opportunities: Scholarships in Brazil - Master