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Paracoccidioides brasiliensis and P. lutzii, thermally dimorphic fungi, are the causative agents of paracoccidioidomycosis (PCM). Paracoccidioides infection occurs when conidia or mycelium fragments are inhaled by the host, which causes the Paracoccidioides cells to transition to the yeast form. The development of disease requires conidia inside the host alveoli to differentiate into yeast cells in a temperature-dependent manner. We describe the presence of a two-component signal transduction system in P. brasiliensis, which we investigated by expression analysis of a hypothetical protein gene (PADG_07579) that showed high similarity with the dimorphism-regulating histidine kinase (DRK1) gene of Blastomyces dermatitidis and Histoplasma capsulatum This gene was sensitive to environmental redox changes, which was demonstrated by a dose-dependent decrease in transcript levels after peroxide stimulation and a subtler decrease in transcript levels after NO stimulation. Furthermore, the higher PbDRK1 levels after treatment with increasing NaCl concentrations suggest that this histidine kinase can play a role as osmosensing. In the mycelium-yeast (M→Y) transition, PbDRK1 mRNA expression increased 14-fold after 24 h incubation at 37°C, consistent with similar observations in other virulent fungi. These results demonstrate that the PbDRK1 gene is differentially expressed during the dimorphic M→Y transition. Finally, when P. brasiliensis mycelium cells were exposed to a histidine kinase inhibitor and incubated at 37°C, there was a delay in the dimorphic M→Y transition, suggesting that histidine kinases could be targets of interest for PCM therapy.

Flavonoids are a class of natural polyphenolic compounds which cannot be synthesized by humans. These substances possess a series of biological properties, acting on biological systems as antioxidants. The purpose of this study was to analyze the properties of certain foods, determining the total flavonoids as well as their antioxidant activity and fat concentration. We evaluated several foods purchased at the local market, with respect to its antioxidant activity, using two experimental models, the discoloration of DPPH˙ radical and ABTS −. Some foods such as pitanga showed antioxidant activity. The lipid content of fatty foods like açaí, cacao and cupuaçú was determined. Other foods, including pitanga, açaí, cacao and cupuaçú, were evaluated for flavonoid content and antioxidant activity using multivariate statistical analysis (PCA) as a statistical tool to evaluate the correlation between these two parameters. As samples with ED50 up to 500 µg/mL show promising antioxidant activity, several Brazilian fruit and vegetables could be consumed to this end, with a good correlation between flavonoid content and antioxidant activity in most samples. The daily dose of different types of food for antioxidant activity has been calculated based on these results.

S-Nitroso-Proteome of Paracoccidioides brasiliensisIn addition, we detected that the transnitrosylation/denitrosylation redox signaling are preserved in this fungus. Finally, this work may help to uncover the beneficial and antifungal properties of NO in the P. brasiliensis and point to useful targets for the development of antifungal drugs.

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The dichotomous behavior of superoxide dismutase-2 (SOD2) in cancer biology has long been acknowledged and more recently linked to different posttranslational forms of the enzyme. However, a distinctive activity underlying its tumor-promoting function is yet to be described. Here, we report that acetylation, one of such posttranslational modifications (PTMs), increases SOD2 affinity for iron, effectively changing the biochemical function of this enzyme from that of an antioxidant to a demethylase. Acetylated, iron-bound SOD2 localizes to the nucleus, promoting stem cell gene expression via removal of suppressive epigenetic marks such as H3K9me3 and H3K927me3. Particularly, H3K9me3 was specifically removed from regulatory regions upstream of Nanog and Oct-4, two pluripotency factors involved in cancer stem cell reprogramming. Phenotypically, cells expressing nucleus-targeted SOD2 (NLS-SOD2) have increased clonogenicity and metastatic potential. FeSOD2 operating as H3 demethylase requires H 2 O 2 as substrate, which unlike cofactors of canonical demethylases (i.e., oxygen and 2-oxoglutarate), is more abundant in tumor cells than in normal tissue. Therefore, our results indicate that FeSOD2 is a demethylase with unique activities and functions in the promotion of cancer evolution toward metastatic phenotypes.

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