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

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...

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Bibliographic Details
Published in:Chemical reviews 2021-05, Vol.121 (9), p.5193-5239
Main Authors: Klebba, Phillip E, Newton, Salete M. C, Six, David A, Kumar, Ashish, Yang, Taihao, Nairn, Brittany L, Munger, Colton, Chakravorty, Somnath
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
Antibiotics
Bacteria
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Eukaryotes
Ferric Compounds - chemistry
Ferric Compounds - metabolism
Ferritin
Gram-Negative Bacteria - drug effects
Gram-Negative Bacteria - metabolism
Gram-Negative Bacteria - pathogenicity
Humans
Immunology
Infectious diseases
Iron
Iron - chemistry
Iron - metabolism
Membrane Proteins - chemistry
Membrane Proteins - metabolism
Microorganisms
Models, Molecular
Pathogenesis
Pathogens
Proteins
Scavenging
Sequestering
Siderophores - chemistry
Siderophores - metabolism
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Summary: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.
ISSN:0009-2665
1520-6890
1520-6890
DOI:10.1021/acs.chemrev.0c01005