Metabolic and Phenotypic Changes Induced during N-Acetylglucosamine Signalling in the Fungal Pathogen Candida...

The human commensal yeast Candida albicans is pathogenic and results in a variety of mucosal and deep tissue problems when the host is immunocompromised. Candida exhibits enormous metabolic flexibility and dynamic morphogenetic transition to survive under host niche environmental conditions and to cause virulence. The amino sugar N-acetylglucosamine (GlcNAc) available at the host infection sites, apart from acting as an extremely good carbon and nitrogen source, also induces cellular signalling in this pathogen. In C. albicans, GlcNAc performs multifaceted roles, including GlcNAc scavenging, GlcNAc import and metabolism, morphogenetic transition (yeast-hyphae and white-opaque switch), GlcNAc-induced cell death (GICD), and virulence. Understanding the molecular mechanism(s) involved in GlcNAc-induced cellular processes has become the main focus of many studies. In the current study, we focused on GlcNAc-induced metabolic changes associated with phenotypic changes. Here, we employed gas chromatography-mass spectrometry (GC-MS), which is a high-throughput and sensitive technology, to unveil global metabolomic changes that occur in GlcNAc vs. glucose grown conditions in Candida cells. The morphogenetic transition associated with metabolic changes was analysed by high-resolution field emission scanning electron microscopy (FE-SEM). Metabolite analysis revealed the upregulation of metabolites involved in the glyoxylate pathway, oxidative metabolism, and fatty acid catabolism to probably augment the synthesis of GlcNAc-induced hypha-specific materials. Furthermore, GlcNAc-grown cells showed slightly more sensitivity to amphotericin B treatment. These results all together provide new insights into the development of antifungal therapeutics for the control of candidiasis in humans.