CTR9 affects virulence of Candida albicans by regulating methionine metabolism

Project Abstract : Paf1C is a general transcription regulator and is associated with various human diseases. One of its subunits, CTR9, is known as a structurally and functionally core component of Paf1C. While its role in higher eukaryotes have been researched, the association between the core component and human fungal pathogen is not fully understood yet. During pre-infection process, Candida albicans adheres to the surface of hosts and sufficiently grows as the circular form. Under immune deficiency condition, C. albicans enters into the infection process and forms hyphae. Here, we performed virulence tests and transcriptome analysis to identify the role of CTR9 in two infection stages. In pre-infection process, CTR9 regulates basic cellular processes and metabolism, affecting cell growth. Of metabolic processes, methionine biosynthetic genes are significantly dependent on CTR9. This pathway hardly affects cell abundance for pre-infection stage, but has considerable effect on hyphal formation during infection stage. Therefore, it shows that methionine biosynthetic pathway mediated by CTR9 is essential for pathogenesis of C. albicans. Sample number (1-12): We performed RNA-seq with WT, Δctr9, Δleo1, and Δcdc73 strains. Experiments were performed in duplicates. RNA-seq using WT and Δctr9 was performed under yeast and hyphae inducing conditions, whereas RNA-seq using Δleo1 and Δcdc73 was performed only under hyphae inducing conditions. Yeast condition; WT (1,2) and Δctr9 (3,4). Hyphae induction condition: WT (5,6), Δctr9 (7,8), Δleo1 (9,10), and Δcdc73 (11,12)