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Published on: June 13, 2021
The role of the Mediator complex in fungal pathogenesis and response to antifungal agents
James O'Connor-Moneley1, Leenah Alaalm1, Gary P Moran1
1Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin, Ireland.
Abstract:
Mediator is a complex of polypeptides that plays a central role in the recruitment of RNA polymerase II to promoters and subsequent transcriptional activation in eukaryotic organisms. Studies have now shown that Mediator has a role in regulating expression of genes implicated in virulence and antifungal drug resistance in pathogenic fungi. The roles of specific Mediator subunits have been investigated in several species of pathogenic fungi, particularly in the most pathogenic yeast Candida albicans. Uniquely, pathogenic yeast also present several interesting examples of divergence in Mediator structure and function, most notably in C. glabrata, which possesses two orthologues of Med15, and in C. albicans, which has a massively expanded family of Med2 orthologues known as the TLO gene family. This review highlights specific examples of recent progress in characterizing the role of Mediator in pathogenic fungi.
Insights
Mediator complex regulates genes for virulence and drug resistance in pathogenic fungi. Research explores unique Mediator subunit roles and structural divergence in species like Candida albicans.
Area of Science:
- Molecular Biology
- Mycology
- Genetics
Background:
- The Mediator complex is crucial for RNA polymerase II recruitment and transcriptional activation in eukaryotes.
- Recent studies reveal Mediator's role in regulating virulence and antifungal drug resistance genes in pathogenic fungi.
Approach:
- This review synthesizes recent findings on Mediator subunit functions in pathogenic fungi.
- Focuses on specific examples, particularly in Candida albicans and Candida glabrata.
Key Points:
- Mediator subunits control gene expression vital for fungal pathogenicity.
- Pathogenic fungi exhibit unique Mediator structures, such as duplicated Med15 in C. glabrata and expanded TLO gene family (Med2 orthologues) in C. albicans.
- Investigating Mediator provides insights into antifungal drug resistance mechanisms.
Conclusions:
- Understanding Mediator's role in pathogenic fungi is key to developing novel antifungal strategies.
- Divergence in Mediator structure suggests species-specific adaptations in virulence and drug resistance.
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