Role of Mediator in virulence and antifungal drug resistance in pathogenic fungi.

ABSTRACT

Mediator complex has recently emerged as an important regulator of gene expression in pathogenic fungi. Mediator is a multi-subunit complex of polypeptides involved in transcriptional activation in eukaryotes, with roles including preinitiation complex (PIC) assembly and chromatin remodeling. Within the last decade, Mediator has been shown to play an integral role in regulating virulence gene expression and drug resistance in human fungal pathogens. In some fungi, specific Mediator subunits have been shown to be required for virulence. In Candida species, duplication and expansion of Mediator subunit encoding genes has occurred on at least three occasions (CgMED15 in C. glabrata and MED2/TLO in C. albicans and C. dubliniensis) suggesting important roles for Mediator in the evolution of these pathogens. This review summarises recent developments in our understanding of Mediator in fungal pathogens and the potential for the development of therapeutic drugs to target Mediator functions.