Role of Amino Acid Metabolism in the Virulence of Human Pathogenic Fungi

The success of Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans as fungal pathogens depends on their rapid adaptation to host microenvironments, through metabolic remodeling, stress resistance, and expression of virulence determinants. Amino acids represent an abundant nitrogen and carbon source within the host; however, their acquisition by fungi is a very complex process that interconnects several sensory and uptake systems and downstream pathways. In this review, we will summarize the current knowledge concerning this topic, identify gaps or discrepancies, and discuss future research directions. Aside from supporting basic cellular functions, the utilization of many amino acids has a direct effect on fungal pathogenicity by triggering key virulence traits, including hyphal morphogenesis and biofilm growth in C. albicans, capsule formation in C. neoformans, and melanization in A. fumigatus. Although many components of amino acid sensing and metabolism are fungal specific, their importance in infection and potential as candidates for antifungal drug development require further investigation.