Harnessing Iron Acquisition Machinery to Target Enterobacteriaceae

J Infect Dis. 2021 Jun 16;223(12 Suppl 2):S307-S313. doi: 10.1093/infdis/jiaa440.


Infections caused by Gram-negative bacteria can be challenging to treat due to the outer membrane permeability barrier and the increasing emergence of antibiotic resistance. During infection, Gram-negative pathogens must acquire iron, an essential nutrient, in the host. Many Gram-negative bacteria utilize sophisticated iron acquisition machineries based on siderophores, small molecules that bind iron with high affinity. In this review, we provide an overview of siderophore-mediated iron acquisition in Enterobacteriaceae and show how these systems provide a foundation for the conceptualization and development of approaches to prevent and/or treat bacterial infections. Differences between the siderophore-based iron uptake machineries of pathogenic Enterobacteriaceae and commensal microbes may lead to the development of selective "Trojan-horse" antimicrobials and immunization strategies that will not harm the host microbiota.

Keywords: Enterobacteriaceae; Gram-negative bacteria; iron; microcins; siderophores.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism*
  • Bacteriocins / metabolism
  • Bacteriocins / pharmacology
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / growth & development
  • Enterobacteriaceae / metabolism
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / growth & development
  • Gram-Negative Bacteria / metabolism
  • Humans
  • Immunization
  • Iron / metabolism*
  • Microbiota / drug effects
  • Siderophores / immunology
  • Siderophores / metabolism*


  • Anti-Bacterial Agents
  • Bacteriocins
  • Siderophores
  • microcin
  • Iron