Identification And Characterization Of Candida Albicans CaSCH9 Gene

The target of rapamycin complex 1 (TORC1) is the central controller of growth in eukaryotic cells. TORC1 could directly phosphorylate the protein serine/threonine kinase ScSch9p and regulates ribosome biogenesis, translation initiation and entry into the G0 phase through ScSch9p in S. cerevisiae. Deletion of either ScTOR1 or ScSCH9 increases the lifespan of yeast cells. ScSch9p is involved in nitrogen and carbon source-dependent regulation of ribosomal proteins and stress-responsive genes. Like rapamycin-treated cells, cells deleted for ScSCH9 show nuclear localization and activation of the ScRim15p kinase and decreased expression of genes required for ribosome biogenesis.Candida albicans remains the most important fungal pathogen in humans and can lead to life-threatening systemic infection in immunocompromised patients. Several components of the TOR signaling pathway have been identified and characterized in C. albicans. Similar to mammalian and plant cells, C. albicans cells have only one single TOR homolog in the genome. The antifungal activity of rapamycin toward C. albicans has been shown to be mediated via its complex with FKBP12 and TOR kinase homologs. These indicate that TOR signaling is highly conserved in C. albicans.In this study, we demonstrate that Candida albicans cells with CaSCH9 deleted have reduced cell sizes and show a delayed log-phase growth. In addition, deletion of CaSCH9 renders C. albicans cells sensitive to rapamycin and caffeine. Similar to ScSCH9, deletion of CaSCH9 also causes C. albicans cells to become sensitive to cations, but does not lead to a defect in the utilization of galactose. Furthermore, deletion of CaSCH9 affects the filamentation of C. albicans cells and attenuates the virulence in a mouse mode of systemic candidiasis. Therefore, CaSch9p is an important regulator for the cell growth, filamentation and virulence of this human fungal pathogen.