title: Exploring potential virulence regulators in Paracoccidioides brasiliensis isolates of varying virulence through quantitative proteomics.
abstract: Few virulence factors have been identified for Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis. In this study, we quantitatively evaluated the protein composition of P. brasiliensis in the yeast phase using minimal and rich media to obtain a better understanding of its virulence and to gain new insights into pathogen adaptation strategies. This analysis was performed on two isolates of the Pb18 strain showing distinct infection profiles in B10.A mice. Using liquid chromatography/tandem mass spectrometry (LC-MS/MS) analysis, we identified and quantified 316 proteins in minimal medium, 29 of which were overexpressed in virulent Pb18. In rich medium, 29 out of 295 proteins were overexpressed in the virulent fungus. Three proteins were found to be up-regulated in both media, suggesting the potential roles of these proteins in virulence regulation in P. brasiliensis. Moreover, genes up-regulated in virulent Pb18 showed an increase in its expression after the recovery of virulence of attenuated Pb18. Proteins up-regulated in both isolates were grouped according to their functional categories. Virulent Pb18 undergoes metabolic reorganization and increased expression of proteins involved in fermentative respiration. This approach allowed us to identify potential virulence regulators and provided a foundation for achieving a molecular understanding of how Paracoccidioides modulates the host-pathogen interaction to its advantage.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo , Rua Mirassol, 207, São Paulo, 04044-010 SP, Brazil.
authors.forename: Daniele G
authors.initials: DG
authors.lastname: Castilho
authors.forename: Alison F A
authors.initials: AF
authors.lastname: Chaves
authors.forename: Patricia
authors.initials: P
authors.lastname: Xander
authors.forename: André
authors.initials: A
authors.lastname: Zelanis
authors.forename: Eduardo S
authors.initials: ES
authors.lastname: Kitano
authors.forename: Solange M T
authors.initials: SM
authors.lastname: Serrano
authors.forename: Alexandre K
authors.initials: AK
authors.lastname: Tashima
authors.forename: Wagner L
authors.initials: WL
authors.lastname: Batista
mesh_terms: D005656:Fungal Proteins / Q000378:metabolism*; D013058:Mass Spectrometry; D010228:Paracoccidioides / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D016133:Polymerase Chain Reaction; D040901:Proteomics; D012331:RNA, Fungal / Q000235:genetics / Q000302:isolation & purification; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D012331:RNA, Fungal
keywords: Paracoccidioides brasiliensis; pathogenic fungus; proteomic analysis; virulence regulators