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Updated: May 18, 2026
06:37
Staphylococcus aureus Growth using Human Hemoglobin as an Iron Source
Published on: February 7, 2013
Multiprotein heme shuttle pathway in Staphylococcus aureus: iron-regulated surface determinant cog-wheel kinetics
Michael T Tiedemann1, David E Heinrichs, Martin J Stillman
1Department of Chemistry, The University of Western Ontario, London, Ontario, Canada, N6A 5B7.
Journal of the American Chemical Society
|September 19, 2012
Summary
This study reveals the mechanism of heme transfer in Staphylococcus aureus, showing how IsdC acts as a central cog-wheel facilitating nutrient acquisition for this pathogen. This research details the kinetics of iron scavenging crucial for bacterial survival.
Area of Science:
- Microbiology
- Biochemistry
- Structural Biology
Background:
- Iron is essential for bacterial survival, necessitating specialized systems for nutrient acquisition.
- The human pathogen Staphylococcus aureus utilizes the iron-regulated surface determinant (Isd) protein system to scavenge heme from hemoglobin.
- While the static interactions of heme-binding are known, the dynamic mechanisms of heme transfer remain largely uncharacterized.
Purpose of the Study:
- To elucidate the mechanistic details of heme transfer within the Staphylococcus aureus Isd system.
- To characterize the kinetics and intermediates involved in the sequential transfer of heme from IsdA to IsdE via IsdC.
- To define the specific role of IsdC in facilitating trans-wall heme transport.
Main Methods:
- Time-resolved mass spectrometry (specifically electrospray mass spectrometry) was employed to monitor protein and heme concentrations.
- Magnetic circular dichroism (MCD) spectroscopy provided complementary data on heme-protein interactions.
- Bimolecular kinetic analysis was performed on the mass spectral data to determine reaction rates.
Main Results:
- The study successfully monitored the concentrations of six protein species involved in trans-wall heme transport.
- Heme transfer from IsdA to IsdC was observed to be rapid, while transfer from IsdC to IsdE was slower.
- IsdC was identified as a crucial intermediary, cycling between heme-bound and unbound states to facilitate efficient heme transfer, acting as a central 'cog-wheel'.
Conclusions:
- The Isd system in Staphylococcus aureus employs a dynamic mechanism for heme scavenging and transport.
- IsdC plays a pivotal role as a central mediator in the sequential transfer of heme, essential for bacterial iron acquisition.
- This mechanistic insight into heme transfer is critical for understanding Staphylococcus aureus pathogenesis and developing targeted interventions.
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