The fungal pathogen Candida glabrata has a well-defined oxidative stress response, is extremely resistant to oxidative stress and can survive inside phagocytic cells. In order to further our understanding of the oxidative stress response in C. glabrata, we characterized the superoxide dismutases (SODs) Cu,ZnSOD (Sod1) and MnSOD (Sod2). We found that Sod1 is the major contributor to total SOD activity and is present in cytoplasm, whereas Sod2 is a mitochondrial protein. Both SODs played a central role in the oxidative stress response but Sod1 was more important during fermentative growth and Sod2 during respiration and growth in non-fermentable carbon sources. Interestingly, C. glabrata cells lacking both SODs showed auxotrophy for lysine, a high rate of spontaneous mutation and reduced chronological lifespan. Thus, our study reveals that SODs play an important role in metabolism, lysine biosynthesis, DNA protection and aging in C. glabrata.

The fungal pathogen Candida glabrata is a haploid asexual yeast. Candida glabrata contains orthologs of the genes that control mating and cell-type identity in other fungi, which encode putative transcription factors localized in the MAT locus in Saccharomyces cerevisiae or MTL in other fungi. Candida glabrata contains three copies of the CgMTL locus but only CgMTL1 correctly expresses the information encoded in it. CgMTL1 can encode the Cg a1 gene ( a information), or the Cg alpha1 and Cg alpha2 genes (alpha information). CgMTL2 contains an identical copy of the Cg a1 gene. CgMTL3 contains an identical copy of the Cg alpha1 gene but a longer variant of the Cg alpha2 gene that we termed Cg alpha3. In S. cerevisiae diploid cells, that express Sc a and Sc alpha information, Sc a1 and Sc alpha2 proteins form a heterodimer, which represses genes expressed only in haploid cells and some genes involved in stress response. We constructed C. glabrata strains that simultaneously express Cg a1 and Cg alpha2 or Cg a1 and Cg alpha3 genes. We did not find any phenotype in these strains when grown under a large variety of stress and nutritional conditions. However, we detected an interaction between Cg a1 and Cg alpha2 but not between Cg a1 and Cg alpha3 by Bimolecular Fluorescence Complementation and co-immunoprecipitation assays.

Arterial hypertension is a highly prevalent chronic disease worldwide, with several etiologies and treatments that may eventually have side effects or result in patients developing tolerance. There is growing interest in traditional medicine and functional foods to isolate biomolecules that could be useful as coadjuvants for treating several aliments. Pitaya, a desert fruit endemic in Mexico, is a rich source of bioactive molecules (betalains and phenolic compounds). In this work, the vasorelaxation properties of pitaya juice concentrate and fraction one were investigated using aortic and mesenteric rings from rats. The incubation of rings with pitaya juice concentrate or fraction one induced significant vasorelaxation, independent of the endothelium, and showed resistance to potassium channel blockers. This vasorelaxation was associated with the transmembrane influx of extracellular calcium through the vascular smooth muscle cells, with an inhibitory effect on the voltage-dependent calcium channel currents. Also, 400 mg/mL of pitaya juice concentrate in spontaneous hypertensive rats reduced their blood pressure for 48 h. Phytochemical analyses showed that the primary compounds in F1 were glycosidic in nature, and could be a complex mixture of disaccharides, dimeric disaccharides, or even tetrasaccharides. The glycosidic compounds found in F1 primarily contributed to vasodilatation, establishing a voltage-dependent calcium channel inhibition as a possible molecular target.