Siderophore-dependent iron uptake systems as gates for antibiotic Trojan horse strategies against Pseudomonas aeruginosa

Metallomics. 2014 Mar;6(3):408-20. doi: 10.1039/c3mt00359k. Epub 2014 Jan 31.


Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen responsible for nosocomial infections. The prevalence of antibiotic-resistant P. aeruginosa strains is increasing, necessitating the urgent development of new strategies to improve the control of this pathogen. Its bacterial envelope constitutes of an outer and an inner membrane enclosing the periplasm. This structure plays a key role in the resistance of the pathogen, by decreasing the penetration and the biological impact of many antibiotics. However, this barrier may also be seen as the "Achilles heel" of the bacterium as some of its functions provide opportunities for breaching bacterial defenses. Siderophore-dependent iron uptake systems act as gates in the bacterial envelope and could be used in a "Trojan horse" strategy, in which the conjugation of an antibiotic to a siderophore could significantly increase the biological activity of the antibiotic, by enhancing its transport into the bacterium. In this review, we provide an overview of the various siderophore-antibiotic conjugates that have been developed for use against P. aeruginosa and show that an accurate knowledge of the structural and functional features of the proteins involved in this transmembrane transport is required for the design and synthesis of effective siderophore-antibiotic Trojan horse conjugates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacology
  • Biological Transport
  • Drug Resistance, Bacterial
  • Humans
  • Iron / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / chemistry
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / metabolism*
  • Siderophores / chemistry
  • Siderophores / metabolism*


  • Anti-Bacterial Agents
  • Siderophores
  • Iron