期刊
BIOCHEMICAL JOURNAL
卷 463, 期 -, 页码 103-114出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20140598
关键词
adherence; Candida glabrata; common in fungal extracellular membranes (CFEM) domain; haemolysin; high-affinity iron uptake; intracellular iron content; virulence
资金
- Department of Biotechnology, Government of India [BT/PR13289/BRB/10/745/2009, BT/PR5145/MED/29/470/2012, BT/PR7388/MED/29/650/ 2012]
- Centre for DNA Fingerprinting and Diagnostics, Hyderabad
- Council of Scientific and Industrial Research
Iron is an essential nutrient for all living organisms and human pathogens employ a battery of factors to scavenge iron from the high-affinity iron-binding host proteins. In the present study, we have elucidated, via a candidate gene approach, major iron acquisition and homoeostatic mechanisms operational in an opportunistic human fungal pathogen Candida glabrata. Phenotypic, biochemical and molecular analysis of a set of 13 C. glabrata strains, deleted for proteins potentially implicated in iron metabolism, revealed that the high-affinity reductive iron uptake system is required for utilization of alternate carbon sources and for growth under both in vitro iron-limiting and in vivo conditions. Furthermore, we show for the first time that the cysteine-rich CFEM (common in fungal extracellular membranes) domain-containing cell wall structural protein, CgCcw14, and a putative haemolysin, CgMam3, are essential for maintenance of intracellular iron content, adherence to epithelial cells and virulence. Consistent with their roles in iron homoeostasis, mitochondrial aconitase activity was lower and higher in mutants disrupted for high-affinity iron transport, and haemolysin respectively. Additionally, we present evidence that the mitochondrial frataxin, CgYfh1, is pivotal to iron metabolism. Besides yielding insights into major in vitro and in vivo iron acquisition strategies, our findings establish high-affinity iron uptake mechanisms as critical virulence determinants in C. glabrata.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据