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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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