Characterization and Regulation of the Trehalose Synthesis Pathway and Its Importance in the Pathogenicity of Cryptococcus neoformans

摘要: The disaccharide trehalose has been found to play diverse roles, from energy source stress protectant, and this sugar is in organisms as bacteria, fungi, plants, invertebrates but not mammals. Recent studies the pathobiology of Cryptococcus neoformans identified presence a functioning pathway during infection suggested its importance for C. survival host. Therefore, we created null mutants trehalose-6-phosphate (T6P) synthase (TPS1), trehalose-6-phophate phosphatase (TPS2), neutral trehalase (NTH1) genes. We that both TPS1 TPS2 are required high-temperature (37°C) growth glycolysis block at results apparent toxic accumulation T6P, which makes enzyme fungicidal target. Sorbitol suppresses defect tps1 tps2 37°C, supports hypothesis these sugars (trehalose sorbitol) act primarily protectants proteins membranes exposure high temperatures neoformans. essential nature disease was confirmed when mutant strain be avirulent rabbits mice. Furthermore, system invertebrate elegans, vivo temperature no longer an environmental factor, attenuation virulence still noted with mutant, involved more host mechanisms than simply stresses glycolysis. These previous other pathogenic fungi support view selective target use antifungal development.