Ribosome profiling reveals differences in global translational vs transcriptional gene expression changes during...

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, 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 upregulated or downregulated 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.IMPORTANCEThe major human fungal pathogen Candida albicans is known to form biofilms or complex aggregated microbial communities encased in an extracellular matrix. These biofilms allow C. albicans to escape detection by the immune system as well as resist a variety of antifungal drugs. In this study, we define the first global profile of genes that show altered translation during C. albicans biofilm formation. These genes are involved in a variety of key cellular processes, including polarized growth, pathogenesis, transport, protein synthesis, cell cycle, plasma membrane, signal transduction, and secretion. Interestingly, while similar classes of genes are induced at both the transcriptional and translational levels during early C. albicans biofilm formation, we observed very little overlap among specific genes with altered transcription and translation. Our results suggest that C. albicans biofilm formation is controlled by distinct translational mechanisms, which could potentially be targeted by novel antifungal drugs.