Analysis of Mutants Defective in the Cdk8 Module of Mediator Reveal Links between Metabolism and Biofilm Formation

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Candida albicans is currently one of the most common causes of nosocomial infections, and causes diseases ranging from oral thrush to life-threatening systemic infections. C. albicans readily forms biofilms on implanted devices, such as catheters and dentures, and biofilms are associated with increased risk of systemic infections and resistance to antifungals. We previously showed that biofilm formation positively correlates with oxidative metabolism. Here, we show that respiration, wrinkled colony formation, biofilm formation, and resistance to the inhibitory effects of pyocyanin were increased when the Cdk8 module of Mediator, a co-regulator of transcription, was compromised. Cdk8 module mutants all exhibited differences in basal metabolism that were indicative of increased metabolic activity. Furthermore, using these strains, we showed a direct correlation between the inhibition of respiratory activity, in the absence of growth defects, and inhibition of biofilm formation, supporting a model in which C. albicans metabolism and morphology are linked. The human Cdk8 module is currently being investigated as a target for cancer chemotherapy, and thus an understanding of the consequences or potential benefits of inhibiting this module is required.

Vyšlo v časopise: Analysis of Mutants Defective in the Cdk8 Module of Mediator Reveal Links between Metabolism and Biofilm Formation. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004567
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004567

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