Abstract
The TOR (target of rapamycin) kinase signaling pathway plays an important role in a wide variety of cell functions. In mammals, fly and fission yeast, the TOR kinase is controlled by signal components, including Rheb, a new member of the small G-proteins of Ras superfamily, which has been identified in most of model organism and involved in many cell functions. Moreover, the Rheb homologue in the human fungal pathogen, Aspergillus fumigatus, is involved in the virulence of this pathogen. In this study, the Rheb homologues in the fungal pathogen Candida albicans, RHB1 was identified. To gain insight into the function of these genes, the deletion strains of RHB1 was generated. In comparisons of the mutant to wild type strains, RHB1 deletion mutant showed enhanced sensitivities to potent anti-TOR kinase drug rapamycin, suggesting RHB1 correlated and has positive effect in TOR-like pathway in C. albicans. Further studies indicated RHB1 is involved in yeast-hyphae transition which responded to nitrogen starvation via a sensor protein Mep2, the downstream target of TOR signaling pathway. Moreover, RHB1 is involved in cell wall integrity pathway and transmitted signals through TOR kinase and downstream MAP kinase, MKC1. Finally, RHB1 alters C. albicans virulence in a mouse model of systemic infection. Together, this study reveals a novel signaling pathway and provides insights to correlate environmental signaling and C. albicans pathogeneis.