Iron Acquisition and Metabolism as a Promising Target for Antimicrobials (Bottlenecks and Opportunities): Where Do We Stand?

Int J Mol Sci. 2023 Mar 24;24(7):6181. doi: 10.3390/ijms24076181.

Abstract

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) infections is one of the most crucial challenges currently faced by the scientific community. Developments in the fundamental understanding of their underlying mechanisms may open new perspectives in drug discovery. In this review, we conducted a systematic literature search in PubMed, Web of Science, and Scopus, to collect information on innovative strategies to hinder iron acquisition in bacteria. In detail, we discussed the most interesting targets from iron uptake and metabolism pathways, and examined the main chemical entities that exhibit anti-infective activities by interfering with their function. The mechanism of action of each drug candidate was also reviewed, together with its pharmacodynamic, pharmacokinetic, and toxicological properties. The comprehensive knowledge of such an impactful area of research will hopefully reflect in the discovery of newer antibiotics able to effectively tackle the antimicrobial resistance issue.

Keywords: antimicrobial resistance; immunity; metallostasis; siderophores; virulence factors.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Anti-Infective Agents* / pharmacology
  • Anti-Infective Agents* / therapeutic use
  • Bacteria
  • Drug Discovery
  • Iron

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Iron