title: [Iron and invasive fungal infection].
abstract: Iron is an essential factor for both the growth and virulence of most of microorganisms. As a part of the innate (or nutritional) immune system, mammals have developed different mechanisms to store and transport this element in order to limit free iron bioavailability. To survive in this hostile environment, pathogenic fungi have specific uptake systems for host iron sources, one of the most important of which is based on the synthesis of siderophores-soluble, low-molecular-mass, high-affinity iron chelators. The increase in free iron that results from iron-overload conditions is a well-established risk factor for invasive fungal infection (IFI) such as mucormycosis or aspergillosis. Therefore, iron chelation may be an appealing therapeutic option for these infections. Nevertheless, deferoxamine -the first approved iron chelator- paradoxically increases the incidence of IFI, as it serves as a xeno-siderophore to Mucorales. On the contrary, the new oral iron chelators (deferiprone and deferasirox) have shown to exert a deleterious effect on fungal growth both in vitro and in animal models. The present review focuses on the role of iron metabolism in the pathogenesis of IFI and summarises the preclinical data, as well as the limited clinical experience so far, in the use of new iron chelators as treatment for mucormycosis and invasive aspergillosis.
authors.affiliation: Servicio de Medicina Interna, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense, Madrid, España.
authors.forename: Florencio
authors.initials: F
authors.lastname: Álvarez
authors.forename: Mario
authors.initials: M
authors.lastname: Fernández-Ruiz
authors.forename: José María
authors.initials: JM
authors.lastname: Aguado
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000009:adverse effects; D004198:Disease Susceptibility; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005656:Fungal Proteins / Q000502:physiology; D016469:Fungemia / Q000188:drug therapy / Q000378:metabolism*; D005658:Fungi / Q000187:drug effects / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use; D019190:Iron Overload / Q000150:complications / Q000378:metabolism; D023421:Models, Animal; D015394:Molecular Structure; D009090:Mucorales / Q000187:drug effects / Q000378:metabolism; D009091:Mucormycosis / Q000188:drug therapy / Q000378:metabolism; D010084:Oxidation-Reduction; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use; D017262:Siderophores / Q000502:physiology; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D001565:Benzoates; D005656:Fungal Proteins; D007502:Iron Chelating Agents; D011728:Pyridones; D017262:Siderophores; D014230:Triazoles; D000077543:Deferiprone; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox
keywords: Aspergillosis; Aspergilosis; Deferasirox; Deferiprona; Deferiprone; Deferoxamina; Deferoxamine; Iron chelators; Mucormicosis; Mucormycosis; Quelantes del hierro