Invasive Candida infections are an important growing medical concern and treatment options are limited to a few antifungal drug classes, with limited efficacies depending on the infecting organism. In this scenario, invasive infections caused by multiresistant Candida auris are emerging in several places around the world as important healthcare-associated infections. As antimicrobial peptides (AMPs) exert their activities primarily through mechanisms involving membrane disruption, they have a lower chance of inducing drug resistance than general chemical antimicrobials. Interestingly, we previously described the potent candicidal effect of a rattlesnake AMP, crotamine, against standard and treatment-resistant clinical isolates, with no hemolytic activity. We evaluated the antifungal susceptibility of several Candida spp. strains cultured from different patients by using the Clinical and Laboratory Standards Institute (CLSI) microdilution assay, and the antifungal activity of native crotamine was evaluated by a microbial growth inhibition microdilution assay. Although all Candida isolates evaluated here showed resistance to amphotericin B and fluconazole, crotamine (40–80 µM) exhibited in vitro activity against most isolates tested. We suggest that this native polypeptide from the South American rattlesnake Crotalus durissus terrificus has potential as a structural model for the generation of a new class of antimicrobial compounds with the power to fight against multiresistant Candida spp.

The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. Metabolomic profiling, employing 1H-NMR, 1H-NMR T2-edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder (n = 26) compared with healthy volunteers (n = 50) was performed. The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-l-phenyl alanine, N-acetyl-l-aspartyl-l-glutamic acid, l-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.

O triptofano (TRP) é um aminoácido essencial, encontrado no plasma principalmente ligado à albumina, e com apenas uma pequena fração encontrada na forma livre. Ao atravessar a barreia hematoencefálica, seus metabólitos exercem diferentes ações no sistema nervoso central. Importantes metabólitos neuroativos resultantes do metabolismo do TRP (como a serotonina, melatonina, 3-hidroxiquinurenina, ácido quinolínico e quinurênico, dentre outros) têm sido associados a doenças neurodegenerativas como o Mal de Alzheimer, a doença de Huntington, o transtorno bipolar (TB) e a esquizofrenia (SCZ). Além disto, há também relatos sobre a sua relação com a depressão, as doenças inflamatórias, diversas alergias e com doenças infecciosas. O objetivo deste trabalho foi reunir informações recentes e atualizadas sobre o que se sabe sobre papel do TRP e as seus metabólitos, enfatizando a relação desse aminoácido e seus metabólitos na fisiopatologia da SCZ, com enfoque na via das quinureninas e sobretudo suas eventuais associações com as doenças mentais.