Ashraf S Ibrahim1, Brad Spellberg, John Edwards. 1. Division of Infectious Diseases, Harbor-UCLA Medical Center, 1124 West Carson St, RB2, Torrance, CA 90502, USA. Ibrahim@labiomed.org
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: Further investigation and development of iron chelators as adjunctive therapy for mucormycosis is warranted.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: Further investigation and development of iron chelators as adjunctive therapy for mucormycosis is warranted.
Authors: J R Boelaert; M de Locht; J Van Cutsem; V Kerrels; B Cantinieaux; A Verdonck; H W Van Landuyt; Y J Schneider Journal: J Clin Invest Date: 1993-05 Impact factor: 14.808
Authors: Yue Fu; Helen Lee; Mary Collins; Huei-Fung Tsai; Brad Spellberg; John E Edwards; Kyung J Kwon-Chung; Ashraf S Ibrahim Journal: FEMS Microbiol Lett Date: 2004-06-01 Impact factor: 2.742
Authors: Mingfu Liu; Brad Spellberg; Quynh T Phan; Yue Fu; Yong Fu; Amy S Lee; John E Edwards; Scott G Filler; Ashraf S Ibrahim Journal: J Clin Invest Date: 2010-05-17 Impact factor: 14.808