Iron Source Preference and Regulation of Iron Uptake in Cryptococcus neoformans

PLoS Pathogens

Daniel J Kosman¹  Arvinder Singh¹  Anita Sham²  Tianshun Lian²  Won Hee Jung²  James W Kronstad² 

[1] Department of Biochemistry, School of Medicine and Biomedical Sciences, The University at Buffalo, Buffalo, New York, United States of America;The Michael Smith Laboratories, Department of Microbiology and Immunology, and Faculty of Land and Food Systems, University of British Columbia, Vancouver, British Columbia, Canada

关键词: Cryptococcus neoformans;    Gene regulation;    Mouse models;    Saccharomyces cerevisiae;    Heme;    Fungal diseases;    Fungi;    C;    ida albicans;   

DOI  :  10.1371/journal.ppat.0040045

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The level of available iron in the mammalian host is extremely low, and pathogenic microbes must compete with host proteins such as transferrin for iron. Iron regulation of gene expression, including genes encoding iron uptake functions and virulence factors, is critical for the pathogenesis of the fungus Cryptococcus neoformans. In this study, we characterized the roles of the CFT1 and CFT2 genes that encode C. neoformans orthologs of the Saccharomyces cerevisiae high-affinity iron permease FTR1. Deletion of CFT1 reduced growth and iron uptake with ferric chloride and holo-transferrin as the in vitro iron sources, and the cft1 mutant was attenuated for virulence in a mouse model of infection. A reduction in the fungal burden in the brains of mice infected with the cft1 mutant was observed, thus suggesting a requirement for reductive iron acquisition during cryptococcal meningitis. CFT2 played no apparent role in iron acquisition but did influence virulence. The expression of both CFT1 and CFT2 was influenced by cAMP-dependent protein kinase, and the iron-regulatory transcription factor Cir1 positively regulated CFT1 and negatively regulated CFT2. Overall, these results indicate that C. neoformans utilizes iron sources within the host (e.g., holo-transferrin) that require Cft1 and a reductive iron uptake system.

【 授权许可】

CC BY