Global Translational Landscape of the Candida albicans Morphological Transition

Candida albicans is a major human fungal pathogen that represents the fourth leading cause of hospital-acquired bloodstream infections in the U.S. and is associated with high mortality and/or morbidity rates in a wide variety of immunocompromised individuals, including cancer and AIDS patients. While the C. albicans morphological transition from yeast to filamentous cells is required for virulence, considerably little is known about translational mechanisms important for controlling this transition as well as other virulence-related processes in C. albicans and other human fungal pathogens. Using ribosome profiling, we report the first global translational profile associated with C. albicans morphogenesis. Strikingly, many genes involved in pathogenesis, filamentation, response to stress and cell wall organization show reduced translational efficiency (TE). Several of these genes are known to be strongly induced at the transcriptional level, suggesting that a translational fine-tuning mechanism is in place. Using a recently developed ORF-calling method, we have identified a significant number of potential uORFs in genes associated with pathogenesis and at least 57 potential novel ORFs, several of which appear to show altered TE in response to filamentation. Finally, using a novel method for global analysis of ribosome pausing from Ribo-seq data, we demonstrate an enrichment of ribosome pausing sites in C. albicans genes associated with protein synthesis and cell wall functions. Altogether, our results suggest that the C. albicans morphological transition is associated with widespread global translational alterations that do not simply reflect transcriptional changes and affect the expression of many genes associated with virulence-related processes and pathogenesis. Overall design: Examination of gene expression by RNA-seq and Ribo-seq in 1 strain of Candida albicans grown under 2 conditions (YEPD + serum at 37°C (filament-inducing) and YEPD at 30°C (non filament-inducing)). There are three biological replicates for each strain grown under each condition (12 samples total).