The Role of Iron in Staphylococcus aureus Infection and Human Disease: A Metal Tug of War at the Host—Microbe Interface

Madeleine C. van Dijk, Robin M. de Kruijff, Peter Leon Hagedoorn*

*Corresponding author for this work

Research output: Contribution to journalReview articleScientificpeer-review

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Abstract

Iron deficiency anemia can be treated with oral or intravenous Fe supplementation. Such supplementation has considerable effects on the human microbiome, and on opportunistic pathogenic micro-organisms. Molecular understanding of the control and regulation of Fe availability at the host-microbe interface is crucial to interpreting the side effects of Fe supplementation. Here, we provide a concise overview of the regulation of Fe by the opportunistic pathogen Staphylococcus aureus. Ferric uptake regulator (Fur) plays a central role in controlling Fe uptake, utilization and storage in order to maintain a required value. The micro-organism has a strong preference for heme iron as an Fe source, which is enabled by the Iron-regulated surface determinant (Isd) system. The strategies it employs to overcome Fe restriction imposed by the host include: hijacking host proteins, replacing metal cofactors, and replacing functions by non-metal dependent enzymes. We propose that integrated omics approaches, which include metalloproteomics, are necessary to provide a comprehensive understanding of the metal tug of war at the host-microbe interface down to the molecular level.

Original languageEnglish
Article number857237
Number of pages7
JournalFrontiers in Cell and Developmental Biology
Volume10
DOIs
Publication statusPublished - 2022

Keywords

  • ferric uptake regulator
  • heme
  • iron deficiency anemia
  • iron homeostasis
  • iron-regulated surface determinant system
  • MRSA
  • nutritional immunity
  • Staphylococcus aureus

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