期刊
JOURNAL OF INFECTIOUS DISEASES
卷 209, 期 11, 页码 1764-1772出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit817
关键词
Staphylococcus aureus; heme; hemoglobin; iron-regulated surface determinant system; infection; iron; pathogenesis
资金
- US Public Health Service from the National Institute of Allergy and Infection Diseases [AI69233, AI073843]
- American Heart Association Greater Southeast Affiliate Predoctoral Fellowship [09PRE2140221]
- Burroughs Wellcome Fund
Staphylococcus aureus is a Gram-positive pathogen responsible for tremendous morbidity and mortality. As with most bacteria, S. aureus requires iron to cause disease, and it can acquire iron from host hemoglobin. The current model for staphylococcal hemoglobin-iron acquisition proposes that S. aureus binds hemoglobin through the surface-exposed hemoglobin receptor IsdB. IsdB removes heme from bound hemoglobin and transfers this cofactor to other proteins of the Isd system, which import and degrade heme to release iron in the cytoplasm. Here we demonstrate that the individual components of the Isd system are required for growth on low nanomolar concentrations of hemoglobin as a sole source of iron. An in-depth study of hemoglobin binding by IsdB revealed key residues that are required for hemoglobin binding. Further, we show that these residues are necessary for heme extraction from hemoglobin and growth on hemoglobin as a sole iron source. These processes are found to contribute to the pathogenicity of S. aureus in a murine model of infection. Together these results build on the model for Isd-mediated hemoglobin binding and heme-iron acquisition during the pathogenesis of S. aureus infection.
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