Proteomic analysis reveals iron availability alters the metabolic status of the pathogenic fungus paracoccidioides brasiliensis
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2011
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Paracoccidioides brasiliensis is a thermodimorphic fungus and the causative agent of paracoccidioidomycosis (PCM). The
ability of P. brasiliensis to uptake nutrients is fundamental for growth, but a reduction in the availability of iron and other
nutrients is a host defense mechanism many pathogenic fungi must overcome. Thus, fungal mechanisms that scavenge iron
from host may contribute to P. brasiliensis virulence. In order to better understand how P. brasiliensis adapts to iron
starvation in the host we compared the two-dimensional (2D) gel protein profile of yeast cells during iron starvation to that
of iron rich condition. Protein spots were selected for comparative analysis based on the protein staining intensity as
determined by image analysis. A total of 1752 protein spots were selected for comparison, and a total of 274 out of the 1752
protein spots were determined to have changed significantly in abundance due to iron depletion. Ninety six of the 274
proteins were grouped into the following functional categories; energy, metabolism, cell rescue, virulence, cell cycle, protein
synthesis, protein fate, transcription, cellular communication, and cell fate. A correlation between protein and transcript
levels was also discovered using quantitative RT-PCR analysis from RNA obtained from P. brasiliensis under iron restricting
conditions and from yeast cells isolated from infected mouse spleens. In addition, western blot analysis and enzyme activity
assays validated the differential regulation of proteins identified by 2-D gel analysis. We observed an increase in glycolytic
pathway protein regulation while tricarboxylic acid cycle, glyoxylate and methylcitrate cycles, and electron transport chain
proteins decreased in abundance under iron limiting conditions. These data suggest a remodeling of P. brasiliensis
metabolism by prioritizing iron independent pathways.
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PARENTE, Ana F. A. et al. Proteomic analysis reveals iron availability alters the metabolic status of the pathogenic fungus paracoccidioides brasiliensis. Plos One, San Francisco, v. 6, n. 7, p. e22810, 2011.