Translation Regulation in Fungal Pathogens

Candida albicans is an opportunistic infectious yeast. Pathogenicity requires detecting and responding to stress in divergent physiological microenvironments. Under stress, C. albicans undergoes the process of filamentation, shifting from commensal yeast to virulent hyphae. In addition, C albicans can also form biofilms. Under different hyphal-inducing conditions C. albicans activates distinct transcriptional programs. While transcriptional control of hyphal growth has been extensively studied, comparatively little is known about post-transcriptional regulation of this significant morphological shift. We use CRISPR-Cas9, mRNA seq, and ribosome profiling to examine the role that post-transcriptional translation regulation and P-body formation plays in the yeast to hyphae transition. Recently we have found that in lab and clinical strains of C. albicans, mRNA decay factors play distinct roles in regulating cell morphology and that Dhh1 contributes to environmentally appropriate expression of the stress response and hyphal growth. Our work supports distinct requirements for specific mRNA decay factors, bolstering evidence for post-transcriptional regulation of filamentation in C. albicans. We are also applying these methods to study translation regulation in another pathogenic fungus, Cryptococcus neoformans.

Tosiano MA, Lanni F, Mitchell AP, McManus CJ. (2025) Roles of P-body factors in Candida albicans filamentation and stress response. Accepted to PLOS Genetics

Cravener MV, Do E, May G, Zarnowski R, Andes DR, McManus CJ, Mitchell AP. (2023) Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network. PLoS Pathogens

Do E, Cravener MV, Huang MY, May G, McManus CJ, Mitchell AP. (2022) Collaboration between Antagonistic Cell Type Regulators Governs Natural Variation in the Candida albicans Biofilm and Hyphal Gene Expression Network. mBio

Lagree K, Woolford CA, Huang MY, May G, McManus CJ, Solis NV, Filler SG, Mitchell AP. (2020) Roles of Candida albicans Mig1 and Mig2 in glucose repression, pathogenicity traits, and SNF1 essentiality. PLoS Genetics

Huang MY, Woolford CA, May G, McManus CJ, Mitchell AP. (2019) Circuit diversification in a biofilm regulatory network. PLoS Pathogens