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Cited by 150Bacterial Genetics and BiotechnologyEscherichia coli research studiesIron Metabolism and Disorders

Iron Acquisition Systems of Gram-negative Bacterial Pathogens Define TonB-Dependent Pathways to Novel Antibiotics

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Klebba, Phillip E., Newton, Salete M. C., Six, David A., Kumar, Ashish, Yang, Taihao, Nairn, Brittany L., Munger, Colton, Chakravorty, Somnath·2021·Chemical Reviews
DOI 10.1021/acs.chemrev.0c01005PMC PMC8687107
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Abstract

Iron is an indispensable metabolic cofactor in both pro- and eukaryotes, which engenders a natural competition for the metal between bacterial pathogens and their human or animal hosts. Bacteria secrete siderophores that extract Fe3+ from tissues, fluids, cells, and proteins; the ligand gated porins of the Gram-negative bacterial outer membrane actively acquire the resulting ferric siderophores, as well as other iron-containing molecules like heme. Conversely, eukaryotic hosts combat bacterial iron scavenging by sequestering Fe3+ in binding proteins and ferritin. The variety of iron uptake systems in Gram-negative bacterial pathogens illustrates a range of chemical and biochemical mechanisms that facilitate microbial pathogenesis. This document attempts to summarize and understand these processes, to guide discovery of immunological or chemical interventions that may thwart infectious disease.

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Crossref · 10.1021/acs.chemrev.0c01005

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  • Antibiotics that target TonB-dependent pathways may reduce pathogenesis.

    “Consequently, antibiotics that target TonB-dependent pathways may reduce pathogenesis (10).”

    From Siderophore-mediated iron acquisition by <i>Klebsiella pneumoniae</i> (2024) · cites this paper as [10]

  • Abundant evidence links bacterial iron acquisition to virulence and infectious disease.

    “Finally, abundant evidence links bacterial iron acquisition to virulence and infectious disease (10).”

    From Siderophore-mediated iron acquisition by <i>Klebsiella pneumoniae</i> (2024) · cites this paper as [10]

  • Virulent strains encode siderophore biosynthetic operons for the production of Ent, GEnt, Abn, and Ybt and produce cognate receptor LGPs for their OM transport.

    “Virulent strains encode siderophore biosynthetic operons for the production of Ent, GEnt, Abn, and Ybt (1) and produce cognate receptor LGPs for their OM transport [(49); this report].”

    From Siderophore-mediated iron acquisition by <i>Klebsiella pneumoniae</i> (2024) · cites this paper as [49]

  • These basic-acidic side-chain pairs are 90-95% conserved and evolutionarily covariant at comparable positions in dozens of other LGP.

    “These basic–acidic side-chain pairs are 90–95% conserved and evolutionarily covariant at comparable positions in dozens of other LGP ( Klebba et al., 2021 ).”

    From Specificity and mechanism of TonB-dependent ferric catecholate uptake by Fiu (2024) · cites this paper as Klebba et al., 2021

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Research works printed but not linked: 23

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Authors
Klebba, P. E., Newton, S. M. C., Six, D. A., Kumar, A., Yang, T., Nairn, B. L., Munger, C., & Chakravorty, S.
Affiliations
  • Kansas State University (US)
  • VenatoRx Pharmaceuticals (United States) (US)
  • Shorter College (US)
  • University at Buffalo, State University of New York (US)
Corresponding author
Klebba, Phillip E.
ORCID
Venue
Chemical Reviews
Publisher
American Chemical Society (ACS)
Published
2021-03-16
Volume
121
Issue
9
Pages
5193-5239
ISSN
  • 0009-2665 (ISSN-L)
  • 1520-6890
DOI
10.1021/acs.chemrev.0c01005
PMC
PMC8687107
OpenAlex
W3137122686
Semantic Scholar
14397063c4a76947d84d93b98e9630571d57abeb
Cited by
150
References
691
Citations by year
2026: 32 · 2025: 38 · 2024: 26 · 2023: 24 · 2022: 25 · 2021: 5
FWCI
2.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Chemical Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Helmholtz Centre for Ocean Research Kiel (GEOMAR) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Division of Intramural Research, National Institute of Allergy and Infectious Diseases (1R21AI115187-01A1)
  • Defense Threat Reduction Agency (DTRA) (Contract No. HDTRA117C0070)
  • National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) (Contract No. 75N93020C00016.)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
iron acquisition, Gram-negative pathogens, TonB-dependent transporters, siderophores, outer membrane porins, heme acquisition, ferritin, antibiotic discovery, bacterial pathogenesis
MeSH terms
Animals, Anti-Bacterial Agents, Bacterial Proteins, Ferric Compounds, Gram-Negative Bacteria, Humans, Iron, Membrane Proteins, Models, Molecular, Siderophores

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