Iron Assimilation during Emerging Infections Caused by Opportunistic Fungi with emphasis on Mucorales and the Development of Antifungal Resistance

Abstract

Iron is a key transition metal required by most microorganisms and is prominently utilised in the transfer of electrons during metabolic reactions. The acquisition of iron is essential and becomes a crucial pathogenic event for opportunistic fungi. Iron is not readily available in the natural environment as it exists in its insoluble ferric form, i.e., in oxides and hydroxides. During infection, the host iron is bound to proteins such as transferrin, ferritin, and haemoglobin. As such, access to iron is one of the major hurdles that fungal pathogens must overcome in an immunocompromised host. Thus, these opportunistic fungi utilise three major iron acquisition systems to overcome this limiting factor for growth and proliferation. To date, numerous iron acquisition pathways have been fully characterised, with key components of these systems having major roles in virulence. Most recently, proteins involved in these pathways have been linked to the development of antifungal resistance. Here, we provide a detailed review of our current knowledge of iron acquisition in opportunistic fungi, and the role iron may have on the development of resistance to antifungals with emphasis on species of the fungal basal lineage order Mucorales, the causative agents of mucormycosis.