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

Chem Rev. 2021 May 12;121(9):5193-5239. doi: 10.1021/acs.chemrev.0c01005. Epub 2021 Mar 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Ferric Compounds / chemistry
  • Ferric Compounds / metabolism
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / metabolism*
  • Gram-Negative Bacteria / pathogenicity
  • Humans
  • Iron / chemistry
  • Iron / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Siderophores / chemistry
  • Siderophores / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Ferric Compounds
  • Membrane Proteins
  • Siderophores
  • tonB protein, Bacteria
  • Iron