Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment.
OBJECTIVE
Mucormycosis is an increasingly common fungal infection with an unacceptably high mortality despite first-line antifungal therapy. Iron acquisition is a critical step in the causative organisms' pathogenetic mechanism. Therefore, abrogation of fungal iron acquisition is a promising therapeutic strategy to impact clinical outcomes for this deadly disease.


RESULTS
The increased risk of mucormycosis in patients with renal failure receiving deferoxamine iron chelation therapy is explained by the fact that deferoxamine actually acts as a siderophore for the agents of mucormycosis, supplying previously unavailable iron to the fungi. The iron liberated from deferoxamine is likely transported into the fungus by the high-affinity iron permease. In contrast, two other iron chelators, deferiprone and deferasirox, do not supply iron to the fungus and were shown to be cidal against Zygomycetes in vitro. Further, both iron chelators were shown to effectively treat mucormycosis in animal models, and one has been successfully used as salvage therapy for a patient with rhinocerebral mucormycosis.


CONCLUSIONS
Further investigation and development of iron chelators as adjunctive therapy for mucormycosis is warranted.
Ibrahim
Ashraf S
AS
Division of Infectious Diseases, Harbor-UCLA Medical Center, 1124 West Carson St, RB2, Torrance, CA 90502, USA. Ibrahim@labiomed.org
Spellberg
Brad
B
Edwards
John
J
D000818:Animals; D001565:Benzoates / Q000378:metabolism / Q000494:pharmacology; D002614:Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D050296:Microbial Viability; D009090:Mucorales / Q000187:drug effects* / Q000378:metabolism*; D009091:Mucormycosis / Q000188:drug therapy* / Q000382:microbiology*; D011728:Pyridones / Q000378:metabolism / Q000494:pharmacology; D014230:Triazoles / Q000378:metabolism / Q000494:pharmacology
D001565:Benzoates; D002614:Chelating Agents; D011728:Pyridones; D014230:Triazoles; D000077543:Deferiprone; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox