Inter-kingdom metabolic disparities at the human -fungal interface: exploring unique fungal metabolites for selective antifungal targets & lab-based susceptibility markers

Background: Fungal infections have emerged as a major global health challenge, particularly among immunocompromised individuals. Current antifungal therapies are limited by toxicity, resistance, and the close evolutionary relationship between fungi and humans. Unique metabolic pathways present in fungi but absent in humans represent promising targets for selective antifungal therapy. Methods: A literature-based analytical review and laboratory correlation framework were developed to evaluate fungal-specific metabolic pathways. Major pathways analyzed included ergosterol biosynthesis, fungal cell-wall polysaccharide metabolism, siderophore-mediated iron acquisition, and secondary metabolite production. Laboratory susceptibility markers were mapped against metabolic targets using published susceptibility testing methods including broth microdilution, metabolic assays, and molecular markers. Results: Several fungal metabolites were identified as promising antifungal targets including ergosterol intermediates, ?-1,3-glucan synthesis products, chitin derivatives, and siderophore compounds. These metabolites demonstrate strong interkingdom metabolic divergence. Laboratory markers such as ?-D-glucan levels, ergosterol quantification, and siderophore detection may provide measurable indicators of antifungal susceptibility and fungal metabolic activity. Conclusions: Inter-kingdom metabolic differences provide an important framework for identifying selective antifungal targets. Integration of metabolic biomarkers into laboratory susceptibility testing may improve antifungal stewardship and early therapeutic decision-making.