The kinases Hsl101 and Urk1 regulate metabolism of Cryptococcus neoformans.

Cryptococcus neoformans is a significant human fungal pathogen, particularly concerning for immunocompromised individuals. Key kinases, Hsl101 and Urk1, are critical for crossing the blood-brain barrier, although the specific mechanisms by which they do so remain undefined. In this study, we systematically investigate the impact of HSL101 or URK1 deletion on the proteomic and metabolomic profiles of C. neoformans. By generating a deletion mutant for HSL101, we observed profound alterations in the expression levels of 366 proteins and 421 metabolites, highlighting significant disruptions in key biological processes, such as oxidative phosphorylation and ATP synthesis, which are vital for energy production in the cell. Similarly, the deletion of URK1 resulted in significant changes in the expression of 236 proteins and 366 metabolites, particularly affecting pathways related to steroid biosynthesis and starch and sucrose metabolism, which are critical for cellular function and adaptation. These findings shed light on the regulatory roles of Hsl101 and Urk1 in the metabolic pathways of C. neoformans.