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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The high affinity iron permease is a key virulence factor required for Rhizopus oryzae pathogenesis
Molecular Microbiology, Volume 77, No. 3, Year 2010
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Description
Rhizopus oryzae is the most common cause of mucormycosis, an angioinvasive fungal infection that causes more then 50% mortality rate despite first-line therapy. Clinical and animal model data clearly demonstrate that the presence of elevated available serum iron predisposes the host to mucormycosis. The high affinity iron permease gene (FTR1) is required for R. oryzae iron transport in iron-depleted environments. Here we demonstrate that FTR1 is required for full virulence of R. oryzae in mice. We show that FTR1 is expressed during infection in diabetic ketoacidosis (DKA) mice. In addition, we disrupted FTR1 by double cross-over homologous recombination, but multinucleated R. oryzae could not be forced to segregate to a homokaryotic null allele. Nevertheless, a reduction of the relative copy number of FTR1 and inhibition of FTR1 expression by RNAi compromised the ability of R. oryzae to acquire iron in vitro and reduced its virulence in DKA mice. Importantly, passive immunization with anti-Ftr1p immune sera protected DKA mice from infection with R. oryzae. Thus, FTR1 is a virulence factor for R. oryzae, and anti-Ftr1p passive immunotherapy deserves further evaluation as a strategy to improve outcomes of deadly mucormycosis. © 2010 Blackwell Publishing Ltd.
Authors & Co-Authors
Ibrahim, Ashraf S.
United States, Torrance
Harbor-ucla Medical Center
United States, Los Angeles
David Geffen School of Medicine at Ucla
Gebremariam, Teclegiorgis
United States, Torrance
Harbor-ucla Medical Center
Lin, Lin
United States, Torrance
Harbor-ucla Medical Center
Luo, Guanpingsheng
United States, Torrance
Harbor-ucla Medical Center
Husseiny, Mohamed Ibrahim
United States, Torrance
Harbor-ucla Medical Center
Egypt, Zagazig
Faculty of Pharmacy
Skory, Christopher D.
United States, Peoria
Usda Ars National Center for Agricultural Utilization Research
Fu, Yue
United States, Torrance
Harbor-ucla Medical Center
United States, Los Angeles
David Geffen School of Medicine at Ucla
French, Samuel W.
United States, Torrance
Harbor-ucla Medical Center
United States, Los Angeles
David Geffen School of Medicine at Ucla
Edwards, John E.
United States, Torrance
Harbor-ucla Medical Center
United States, Los Angeles
David Geffen School of Medicine at Ucla
Spellberg, Brad J.
United States, Torrance
Harbor-ucla Medical Center
Statistics
Citations: 141
Authors: 10
Affiliations: 4
Identifiers
Doi:
10.1111/j.1365-2958.2010.07234.x
ISSN:
0950382X
e-ISSN:
13652958
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health