Glycerolipid homeostasis in Candida albicans, its role in virulence, and the potential for lipotoxicity as an anti-biofilm therapeutic

Candida albicans is highly adaptable to changes in a given environment, a trait that allows it to colonise and thrive in several niches of the human body as a commensal yeast. An opportunistic pathogen, Candida albicans takes advantage of changes in circumstance to drive pathogenicity and cause infection. A better understanding of how metabolic processes influence the fitness, stress response mechanisms and virulence traits of Candida albicans is an important step in better understanding its interactions with the host, what drives certain pathogenic traits, and thus be able to implement successful treatment regimens. In this work we explored the role that glycerolipid metabolism, or the sequestration and mobilisation of excess fatty acids within lipid droplets, play in Candida albicans virulence traits. We discovered that disruption of the DAG acetyltransferases Dga2 and Lro1 limited hyphal induction, increased sensitivity to cell wall and azole stresses, increased β-glucan exposure leading to more pronounced innate immune responses and an overall reduction in virulence. We also observed a filamentation and polarity defect when disrupting putative triacylglycerol lipase Tgl2, coupled with a significant reduction in virulence. Lastly, we explored the potential for induction of lipotoxicity as an anti-biofilm measure, and determined the monounsaturated fatty acid palmitoleic acid as an efficacious prophylactic to prevent C. albicans biofilms. Overall, this work contributes to the understanding of glycerolipid storage in Candida albicans and uncovers a role for appropriate regulation of glycerolipid metabolism in virulence.