Session 3B: Lectures by Fellows/Associates

Chairperson: Kulinder P Singh, IISER, Mohali

Elucidating the Metabolic Drivers of Fungal Morphogenesis

Fluctuations in nutrient availability are one of the most common challenges encountered by microorganisms. A common strategy employed by microorganisms to adapt to continual changes in nutrient availability is to reversibly transition to alternate cell states better suited for growth and survival in that particular environment. Fungi respond to nutrient fluctuations by undergoing reversible morphological transitions termed ‘fungal morphogenesis’. This allows them to efficiently forage for nutrients, form complex biofilm communities and establish persistent infections in a variety of hosts. Current studies have largely focused on identifying gene regulatory networks that control this phenomenon. However, we lack a complete understanding of the driving metabolic processes behind such cellular decision-making events and how they are regulated. Our lab uses multiple fungal model systems, including Saccharomyces cerevisiae and pathogenic fungi, including Candida albicans and Cryptococcus neoformans, to address this question, as these can reversibly transition from yeast cells to filamentous cells (elongated in morphology) when nutrient levels fluctuate. Although nitrogen limitation is a driver of filamentation in these aforesaid fungi, other key metabolic drivers necessary for fungal morphogenesis have not yet been identified. We show that glucose positively influences filamentation in these fungi (in a concentration-dependent manner), and the ability of these fungi to break down glucose into specific metabolites is critical for fungal morphogenesis. Finally, using pertinent murine infection models, we show that a C. albicans strain that is compromised in metabolizing glucose efficiently is unable to establish persistent infection in a host.