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Staphylococcus aureus heme and siderophore-iron acquisition pathways

  • Brigid S. Conroy
  • Jason C. Grigg
  • Maxim Kolesnikov
  • L. Daniela Morales
  • Michael E. P. MurphyEmail author
Article
  • 210 Downloads

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.

Keywords

Staphylococcus Iron-uptake Siderophore Staphyloferrin Heme-uptake Hemoglobin 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Microbiology and ImmunologyLife Sciences Institute, The University of British ColumbiaVancouverCanada

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