Abstract
Staphylococcus aureus is a versatile opportunistic human pathogen. Infection by this bacterium requires uptake of iron from the human host, but iron is highly restricted in this environment. Staphylococcus aureus iron sufficiency is achieved primarily through uptake of heme and high-affinity iron chelators, known as siderophores. Two siderophores (staphyloferrins) are produced and secreted by S. aureus into the extracellular environment to capture iron. Staphylococcus aureus expresses specific uptake systems for staphyloferrins and more general uptake systems for siderophores produced by other microorganisms. The S. aureus heme uptake system uses highly-specific cell surface receptors to extract heme from hemoglobin and hemoglobin-haptoglobin complexes for transport into the cytoplasm where it is degraded to liberate iron. Initially thought to be independent systems, recent findings indicate that these iron uptake pathways intersect. IruO is a reductase that releases iron from heme and some ferric-siderophores. Moreover, multifunctional SbnI produces a precursor for staphyloferrin B biosynthesis, and also binds heme to regulate expression of the staphyloferrin B biosynthesis pathway. Intersection of the S. aureus iron uptake pathways is hypothesized to be important for rapid adaptation to available iron sources. Components of the heme and siderophore uptake systems are currently being targeted in the development of therapeutics against S. aureus.
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Acknowledgements
MEPM acknowledges support from the Canadian Institutes for Health Research (MOP-49597). BSC received support from a National Sciences and Engineering Research Council CGS-M award.
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Conroy, B.S., Grigg, J.C., Kolesnikov, M. et al. Staphylococcus aureus heme and siderophore-iron acquisition pathways. Biometals 32, 409–424 (2019). https://doi.org/10.1007/s10534-019-00188-2
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DOI: https://doi.org/10.1007/s10534-019-00188-2