Ribosome Profiling Reveals Differences in Global Translational vs. Transcriptional Gene Expression Changes During Early Candida albicans Biofilm Formation

Candida albicans, a major human fungal pathogen, can form biofilms on a variety of inert and biological surfaces. C. albicans biofilms allow for immune evasion, are highly resistant to antifungal therapies, and represent a significant complication for a wide variety of immunocompromised patients in clinical settings. While transcriptional regulators and global transcriptional profiles of C. albicans biofilm formation have been well-characterized, much less is known about translational regulation of this important C. albicans virulence property. Here, using ribosome profiling, we define the first global translational profile of genes that are expressed during early biofilm development in a human fungal pathogen, C. albicans. We show that C. albicans biofilm formation involves altered translational regulation of genes and gene classes associated with protein synthesis, pathogenesis, transport, plasma membrane, polarized growth, the cell cycle, secretion and signal transduction. Interestingly, while similar, but not identical, classes of genes showed transcriptional alterations during early C. albicans biofilm development, we observed very little overlap between specific genes that are up-regulated or down-regulated at the translational vs. transcriptional levels. Our results suggest that distinct translational mechanisms play an important role in regulating early biofilm development of a major human fungal pathogen. These mechanisms, in turn, could serve as potential targets for novel antifungal strategies. C. albicans cells were grown under either biofilm or planktonic conditions using 3 biological replicates. Separate samples from cells grown under each condition were prepared for both Ribo-seq and RNA-seq analysis. Overall there are 12 total samples: 3 replicates of biofilm Ribo-seq, 3 replicates of planktonic Ribo-seq, 3 replicates of biofilm RNA-seq and 3 replicates of planktonic RNA-seq.