Abstract
Candida albicans is an opportunistic fungal pathogen and is responsible for life-threatening systemic infections particularly in immunocompromized patients. In C. albicans, the yeast-to-hypha transition is an important virulence factor and triggered by various environmental cues, including nitrogen availability. In yeast, mammals and C. albicans, the TOR (target of rapamycin) signal transduction pathway regulates cell growth and metabolism in response to environmental signals. The MEP2 gene encodes an ammonium permease and a sensor involving in nitrogen-mediated morphogenesis and is found to be regulated by the TOR signaling. To further investigate the regulation of C. albicans MEP2 expression, we deleted SIT4 and knocked-down TAP42 genes encoding putative downstream effectors of the TOR signaling. Low nitrogen-mediated filamentation was strongly inhibited in both mutants. In addition to MEP2, the MEP1 gene encodes another ammonium permease but Mep1 does not function as a sensor. The levels of MEP1 and MEP2 could not be induced in both mutants in response to ammonium starvation and rapamycin treatment. Moreover, SIT4 and TAP42 seem to induce MEP2 expression through the GATA transcription factors Gln3 and Gat1. However, the level of MEP1 was regulated through Gln3 only under low nitrogen concentration. Tap42 and Sit4 formed a phosphatase complex and also regulated phosphorylation of Npr1 (nitrogen permease reactivator 1), a protein kinase. Together, our results suggest that the Tap42-Sit4 phosphatase complex is essential for filamentous growth and and provide important insights about how C. albicans survives in a nitrogen starvation condition within the host.