Fig 6. Integrative multi-omics profiling revealed new pathways that induce C. albicans hyphal formation in a cAMP-independent manner.

New insights into the mechanisms of hyphal morphogenesis were obtained by performing integrative multi-omics profiling in C. albicans. Genetic changes in PR mutants were identified by performing genome analysis, gene-mapping by CRISPR-Cas9, and transcriptome analysis. These studies showed that gene dosage effects on BCY1 (negative regulator of PKA) and global transcription mechanisms promoted hyphal growth in the absence of cAMP. Integrating transcriptomic and proteomic data revealed that the translation rate of some hyphal regulatory TFs increased dramatically during hyphal induction while their mRNA levels did not, suggesting a special type of translational regulation promotes hyphal growth. Parallel comparisons of protein production and phosphorylation revealed that phosphorylation by Hgc1-Cdc28 kinase and yeast casein kinase 1 (Yck2) increased during hyphal induction, even in the absence of adenylyl cyclase, consistent with genetic studies indicating that these kinases play an important role in hyphal growth. Altogether, these data suggest a new model that various hyphal inducers and TFs are predicted to induce a new physiological state that promotes polarized filamentous growth, in part due to changes in protein phosphorylation.