Exploring Potential Virulence
Regulators in <i>Paracoccidioides brasiliensis</i> Isolates
of Varying Virulence
through Quantitative Proteomics
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Abstract
Few
virulence factors have been identified for <i>Paracoccidioides
brasiliensis</i>, the agent of paracoccidioidomycosis. In this
study, we quantitatively evaluated the protein composition of <i>P. brasiliensis</i> 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 <i>P. brasiliensis</i>. 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 <i>Paracoccidioides</i> modulates the host–pathogen interaction to its advantage