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Newly identified antimicrobial activity of an 8-hydroxyquinoline-based ionophore against multidrug-resistant

Gen Li1,2, Ibrahim M El-Deeb3, Hayden G Whyte1,2

  • 1Australian Infectious Diseases Research Centre, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.

The Journal of Antimicrobial Chemotherapy
|June 3, 2026
PubMed
Abstract

Insights

A novel ionophoroantibiotic (IP antibiotic) 12 shows promise against multidrug-resistant bacteria like Enterococcus faecium and Staphylococcus aureus. This IP antibiotic demonstrates bactericidal activity and efficacy in treating skin infections.

Area of Science:

  • Antimicrobial drug discovery
  • Medicinal chemistry
  • Infectious diseases

Background:

  • Enterococcus faecium and Staphylococcus aureus are opportunistic pathogens.
  • These bacteria exhibit antimicrobial resistance, causing life-threatening infections.
  • New therapeutic strategies are urgently needed.

Purpose of the Study:

  • To synthesize and characterize a novel 8-hydroxyquinoline-based ionophore antibiotic, designated IP-antibiotic 12.
  • To evaluate the activity of IP-antibiotic 12 against multidrug-resistant Gram-positive bacteria.
  • To assess the therapeutic potential of IP-antibiotic 12 in preclinical models.

Main Methods:

  • Synthesis and chemical characterization of IP-antibiotic 12.
  • In vitro testing against multidrug-resistant strains of E. faecium and S. aureus.
  • Evaluation of toxicity profile and resistance emergence potential.
  • In vivo efficacy studies in murine models of skin, systemic, and pulmonary infections.

Main Results:

  • IP-antibiotic 12 demonstrated bactericidal activity against multidrug-resistant E. faecium and S. aureus.
  • The compound showed a low propensity for resistance development and dysregulated bacterial metal homeostasis.
  • IP-antibiotic 12 was effective against S. aureus skin infections as a topical agent and adjunct therapy.
  • Efficacy was not observed in murine models of systemic and pulmonary infections.

Conclusions:

  • IP-antibiotic 12 shows potential as a novel therapeutic for multidrug-resistant Gram-positive bacterial infections.
  • The findings support further development of IP-antibiotic 12 and next-generation analogs.
  • Future research should focus on enhancing in vivo efficacy for systemic applications.

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