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The genus  Paracoccidioides  comprises known fungal pathogens of humans and can be isolated from different infection sites. Metabolic peculiarities in different members of the  Paracoccidioides  led us to perform proteomic studies in the presence of the two-carbon molecule acetate, which predominates in the nutrient-poor environment of the phagosome. To investigate the expression rates of proteins of different members of  Paracoccidioides , including one isolate of  P. lutzii  ( Pb 01) and three isolates of  P. brasiliensis  ( Pb 03,  Pb 339, and  Pb EPM83), using sodium acetate as a carbon source, proteins were quantified using label-free and data-independent liquid chromatography-mass spectrometry. Protein profiles of the isolates were statistically analyzed, revealing proteins that were differentially expressed when the fungus was cultivated in a non-preferential carbon source rather than glucose. A total of 1,160, 1,211, 1,280, and 1,462 proteins were reproducibly identified and relatively quantified in  P. lutzii  and the  P. brasiliensis  isolates  Pb 03,  Pb 339, and  Pb EPM83, respectively. Notably, 526, 435, 744, and 747 proteins were differentially expressed among  P. lutzii  and the  P. brasiliensis  isolates  Pb 03,  Pb 339, and  Pb EPM 83 , respectively, with a fold-change equal to or higher than 1.5. This analysis revealed that reorganization of metabolism occurred through the induction of proteins related to gluconeogenesis, glyoxylic/glyoxylate cycle, response to stress, and degradation of amino acids in the four isolates. The following differences were observed among the isolates: higher increases in the expression levels of proteins belonging to the TCA and respiratory chain in  Pb EPM83 and  Pb 01; increase in ethanol production in  Pb 01; utilization of cell wall components for gluconeogenesis in  Pb 03 and  Pb EPM83; and increased β-oxidation and methylcitrate cycle proteins in  Pb 01and  Pb EPM83. Proteomic profiles indicated that the four isolates reorganized their metabolism in different manners to use acetate as a carbon source.

Differential Metabolism of a Two-Carbon Substrate by Members of the Paracoccidioides Genus