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Role of Ferroxidases in Iron Uptake and Virulence of Cryptococcus neoformans

Authors
Jung, Won HeeHu, GuangganKuo, WayneKronstad, James W.
Issue Date
Oct-2009
Publisher
AMER SOC MICROBIOLOGY
Citation
EUKARYOTIC CELL, v.8, no.10, pp 1511 - 1520
Pages
10
Journal Title
EUKARYOTIC CELL
Volume
8
Number
10
Start Page
1511
End Page
1520
URI
https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/22994
DOI
10.1128/EC.00166-09
ISSN
1535-9778
1535-9786
Abstract
Iron acquisition is a critical aspect of the virulence of many pathogenic microbes, and iron limitation is an important defense mechanism for mammalian hosts. We are examining mechanisms of iron regulation and acquisition in the fungal pathogen Cryptococcus neoformans, and here, we characterize the roles of the ferroxidases Cfo1 and Cfo2. Cfo1 is required for the reductive iron uptake system that mediates the utilization of transferrin, an important iron source for C. neoformans during infection. The virulence of a cfo1 mutant was attenuated in a mouse model of cryptococcosis, and the mutant also displayed increased sensitivities to the antifungal drugs fluconazole and amphotericin B. Wild-type levels of drug sensitivity were restored by the addition of exogenous heme, which suggested that reduced levels of intracellular iron may curtail heme levels and interfere with ergosterol biosynthesis. We constructed green fluorescent protein (GFP) fusion proteins and found elevated expression of Cfo1-GFP upon iron limitation, as well as localization of the fusion to the plasma membrane. Trafficking to this location was disrupted by a defect in the catalytic subunit of cyclic AMP-dependent protein kinase. This result is consistent with findings from studies indicating an influence of the kinase on the expression of protein-trafficking functions in C. neoformans.
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Jung, Won Hee
생명공학대학 (시스템생명공학과)
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