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The Mediator complex is an essential co-regulator of RNA polymerase II that is conserved throughout eukaryotes. Here we present the first study of Mediator in the pathogenic fungus  Candida albicans . We focused on the Middle domain subunit Med31, the Head domain subunit Med20, and Srb9/Med13 from the Kinase domain. The  C. albicans  Mediator shares some roles with model yeasts  Saccharomyces cerevisiae  and  Schizosaccharomyces pombe , such as functions in the response to certain stresses and the role of Med31 in the expression of genes regulated by the activator Ace2. The  C. albicans  Mediator also has additional roles in the transcription of genes associated with virulence, for example genes related to morphogenesis and gene families enriched in pathogens, such as the  ALS  adhesins. Consistently, Med31, Med20, and Srb9/Med13 contribute to key virulence attributes of  C. albicans , filamentation, and biofilm formation; and  ALS1  is a biologically relevant target of Med31 for development of biofilms. Furthermore, Med31 affects virulence of  C. albicans  in the worm infection model. We present evidence that the roles of Med31 and Srb9/Med13 in the expression of the genes encoding cell wall adhesins are different between  S. cerevisiae  and  C. albicans : they are repressors of the  FLO  genes in  S. cerevisiae  and are activators of the  ALS  genes in  C. albicans . This suggests that Mediator subunits regulate adhesion in a distinct manner between these two distantly related fungal species.

The Functions of Mediator in Candida albicans Support a Role in Shaping Species-Specific Gene Expression