RNAi in Candida albicans: adaptation, commensalism and pathogenesis

Fungi living in the human gut must adapt to constantly fluctuating environments, which determine whether they remain harmless commensals or become dangerous pathogens. Understanding the mechanisms behind this adaptation is crucial to combating emerging fungal infections. This proposal focuses on Candida albicans, a common gut commensal capable of transitioning into a life-threatening pathogen. Its ability to adapt to the dynamic gut environment is central to this transition, yet much of the underlying mechanistic basis remains poorly understood. We have recently identified a functional RNA interference (RNAi) pathway in C. albicans, overturning the assumption that this pathway is non-functional in this pathogen. Our unpublished data suggest that RNAi is critical for gut adaptation, reducing its pathogenic potential by enabling immune recognition and maintaining fungal-microbiome balance. By integrating expertise in RNAi and epigenetics (Buscaino – Kent Fungal Group, University of Kent), fungal metabolism and immune interactions (Traven – Monash University), and gut microbial ecology (Foster – University of Oxford), we aim to uncover how RNAi regulates fungal adaptation and shapes interactions between the fungus, host, and microbiome. These findings will provide ground-breaking insights into fungal biology and inform innovative strategies to combat infections and promote gut health.