Iron acquisition mechanisms of human skin-associated fungi

Human skin presents a nutritionally restrictive environment in which iron availability is tightly controlled by epidermal iron recycling, host iron-binding proteins, and nutritional immunity. Thus, skin-associated fungi must acquire iron from limited, often host-sequestered sources. This minireview summarizes current knowledge on iron acquisition systems in the fungal taxa most consistently identified in the human skin mycobiome: Malassezia species, Candida albicans, Candida auris, Rhodotorula mucilaginosa, and dermatophytes. These fungi appear to rely on diverse strategies, including reductive iron uptake, heme and ferritin utilization, and siderophore-mediated iron scavenging. However, our mechanistic understanding differs greatly among species. In C. albicans, several uptake systems have been characterized, but their direct roles in cutaneous colonization versus invasive disease remain unclear. In C. auris, persistent skin colonization is a critical biological feature, but iron sources and uptake pathways supporting its survival, as well as how they intersect with its notorious antifungal resistance, remain largely unresolved. Rhodotorula mucilaginosa and dermatophytes employ siderophore-associated iron acquisition, and yet the relevant transporters and regulatory mechanisms remain poorly characterized. Most notably, despite Malassezia's dominance in the human skin mycobiome and its uncertain status as commensal, pathogen, or both, its iron acquisition strategies remain almost completely unexplored at the functional level. Understanding how skin-associated fungi compete for and acquire iron in the cutaneous environment will provide important insights into fungal commensalism, niche adaptation, and the pathogenic transition.