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Journal of Bacteriology, December 2006, p. 8421-8429, Vol. 188, No. 24
0021-9193/06/$08.00+0     doi:10.1128/JB.01335-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Staphylococcus aureus IsdB Is a Hemoglobin Receptor Required for Heme Iron Utilization{triangledown}

Victor J. Torres,1,{dagger} Gleb Pishchany,1,{dagger} Munir Humayun,2 Olaf Schneewind,3 and Eric P. Skaar1*

Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2605,1 National High Magnetic Field Laboratory and Department of the Geological Sciences, 1800 East Paul Dirac Drive, Florida State University, Tallahassee, Florida 32310,2 Department of Microbiology, University of Chicago, Chicago, Illinois 606373

Received 22 August 2006/ Accepted 5 October 2006

The pathogenesis of human infections caused by the gram-positive microbe Staphylococcus aureus has been previously shown to be reliant on the acquisition of iron from host hemoproteins. The iron-regulated surface determinant system (Isd) encodes a heme transport apparatus containing three cell wall-anchored proteins (IsdA, IsdB, and IsdH) that are exposed on the staphylococcal surface and hence have the potential to interact with human hemoproteins. Here we report that S. aureus can utilize the host hemoproteins hemoglobin and myoglobin, but not hemopexin, as iron sources for bacterial growth. We demonstrate that staphylococci capture hemoglobin on the bacterial surface via IsdB and that inactivation of isdB, but not isdA or isdH, significantly decreases hemoglobin binding to the staphylococcal cell wall and impairs the ability of S. aureus to utilize hemoglobin as an iron source. Stable-isotope-tracking experiments revealed removal of heme iron from hemoglobin and transport of this compound into staphylococci. Importantly, mutants lacking isdB, but not isdH, display a reduction in virulence in a murine model of abscess formation. Thus, IsdB-mediated scavenging of iron from hemoglobin represents an important virulence strategy for S. aureus replication in host tissues and for the establishment of persistent staphylococcal infections.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Vanderbilt University Medical School, 21st Avenue South, Medical Center North, Room A-5211, Nashville, TN 37232. Phone: (615) 343-0002. Fax: (615) 343-7392. E-mail: Eric.Skaar{at}vanderbilt.edu.

{triangledown} Published ahead of print on 13 October 2006.

{dagger} V.J.T. and G.P. contributed equally to this work.

Journal of Bacteriology, December 2006, p. 8421-8429, Vol. 188, No. 24
0021-9193/06/$08.00+0     doi:10.1128/JB.01335-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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