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.

Data in support of quantitative proteomics to identify potential virulence regulators in Paracoccidioides brasiliensis isolates

“…Few virulence factors have been identified in these fungi. This paper describes support data from the quantitative proteomics of Paracoccidioides brasiliensis attenuated and virulent isolates [1] . The protein compositions of two isolates of the Pb18 strain showing distinct infection profiles were quantitatively assessed by stable isotopic dimethyl labeling and proteomic analysis.…”

Subtractive phage display selection for screening and identification of peptide sequences with potential use in serodiagnosis of paracoccidioidomycosis caused by Paracoccidioides brasiliensis

“…This can represent a valuable strategy compared to native antigens currently used in PCM diagnosis, since natural antigenic preparations present great variation depending on the culture medium used, P. brasiliensis growth conditions and isolate used (Castilho et al . ), resulting in conflicting information among laboratories (Vidal et al . ).…”

Serological proteomic biomarkers to identify Paracoccidioides species and risk of relapse.

“…The studies that used a proteomic approach focused on the identification of P. brasiliensis proteins [8][9][10] and P. lutzii [11]; however, they did not evaluate serum proteins from PCM patients.…”