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IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus
Citation
Pishchany, G and Sheldon, JR and Dickson, CF and Alam, MT and Read, TD and Gell, DA and Heinrichs, DE and Skaar, EP, IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus, Journal of Infectious Diseases, 209, (11) pp. 1764-1772. ISSN 0022-1899 (2014) [Refereed Article]
Copyright Statement
Copyright 2013 The Authors
DOI: doi:10.1093/infdis/jit817
Abstract
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. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | Staphylococcus aureus; heme; hemoglobin; iron-regulated surface determinant system; infection; iron; pathogenesis |
| Research Division: | Biological Sciences |
| Research Group: | Biochemistry and Cell Biology |
| Research Field: | Structural Biology (incl. Macromolecular Modelling) |
| Objective Division: | Expanding Knowledge |
| Objective Group: | Expanding Knowledge |
| Objective Field: | Expanding Knowledge in the Biological Sciences |
| Author: | Dickson, CF (Miss Claire Dickson) |
| Author: | Gell, DA (Dr David Gell) |
| ID Code: | 93871 |
| Year Published: | 2014 |
| Web of Science® Times Cited: | 24 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2014-08-20 |
| Last Modified: | 2015-02-11 |
| Downloads: | 0 |
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