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Cited by 31Bacterial Genetics and BiotechnologyIron Metabolism and DisordersEscherichia coli research studies

Ins and Outs: Recent Advancements in Membrane Protein-Mediated Prokaryotic Ferrous Iron Transport

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Brown, Janae B., Lee, Mark A., Smith, Aaron T.·2021·Biochemistry
DOI 10.1021/acs.biochem.1c00586PMC PMC8979593
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Abstract

Iron is an essential nutrient for virtually every living organism, especially pathogenic prokaryotes. Despite its importance, however, both the acquisition and the export of this element require dedicated pathways that are dependent on oxidation state. Due to its solubility and kinetic lability, reduced ferrous iron (Fe 2+ ) is useful to bacteria for import, chaperoning, and efflux. Once imported, ferrous iron may be loaded into apo and nascent enzymes and even sequestered into storage proteins under certain conditions. However, excess labile ferrous iron can impart toxicity as it may spuriously catalyze Fenton chemistry, thereby generating reactive oxygen species and leading to cellular damage. In response, it is becoming increasingly evident that bacteria have evolved Fe 2+ efflux pumps to deal with conditions of ferrous iron excess and to prevent intracellular oxidative stress. In this work, we highlight recent structural and mechanistic advancements in our understanding of prokaryotic ferrous iron import and export systems, with a focus on the connection of these essential transport systems to pathogenesis. Given the connection of these pathways to the virulence of many increasingly antibiotic resistant bacterial strains, a greater understanding of the mechanistic details of ferrous iron cycling in pathogens could illuminate new pathways for future therapeutic developments.

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  • In many bacteria, homeostasis also relies on Fe2+ export, particularly under conditions of high Fe2+ and oxidative stress.

    “In many bacteria, homeostasis also relies on Fe2+ export,136,137 particularly under conditions of high Fe2+ and oxidative stress.138−140”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [136]

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Cited by

Sorted by citations

Authors
Brown, J. B., Lee, M. A., & Smith, A. T.
Affiliations
University of Maryland, Baltimore County (US)
Corresponding author
Smith, Aaron T.
ORCID
Venue
Biochemistry
Publisher
American Chemical Society (ACS)
Published
2021-10-20
Volume
60
Issue
44
Pages
3277-3291
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
DOI
10.1021/acs.biochem.1c00586
PMC
PMC8979593
OpenAlex
W3206639490
Cited by
31
References
17
Citations by year
2026: 5 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 6
FWCI
0.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Division of Chemistry (CHE1844624)
  • National Institute of General Medical Sciences (T32 GM066706)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
Keywords
ferrous iron transport, Fenton reaction, oxidative stress, bacterial virulence, antibiotic resistance, iron chaperone, iron storage protein
MeSH terms
Anti-Bacterial Agents, Bacteria, Biological Transport, Catalysis, Homeostasis, Iron, Kinetics, Membrane Proteins, Oxidation-Reduction, Prokaryotic Cells, Solubility, Virulence, Ion Transport, Reactive Oxygen Species, Oxidative Stress, Membrane Transport Proteins

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