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Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
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Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System

Published on: January 5, 2024

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An ionophore breaks the multi-drug-resistance of Acinetobacter baumannii

David M P De Oliveira1, Mark J Walker1

  • 1The University of Queensland, School of Chemistry and Molecular Biosciences, Australian Infectious Diseases Research Centre, Brisbane, QLD, Australia.

Microbial Cell (Graz, Austria)
|March 16, 2022
PubMed

Insights

The 8-hydroxyquinoline ionophore PBT2 resensitizes multi-drug resistant Acinetobacter baumannii to tetracycline antibiotics. PBT2 combined with tetracyclines shows promise for treating Acinetobacter baumannii pulmonary infections.

Area of Science:

  • Infectious Diseases
  • Microbiology
  • Pharmacology

Background:

  • Multi-drug resistant Acinetobacter baumannii is a significant cause of hospital-acquired infections, particularly ventilator-associated pneumonia.
  • Secondary Acinetobacter baumannii infections increase mortality risk in COVID-19 patients requiring mechanical ventilation.

Purpose of the Study:

  • To investigate the potential of the 8-hydroxyquinoline ionophore PBT2 as a resistance breaker for Acinetobacter baumannii.
  • To evaluate the efficacy of PBT2 in combination with tetracycline-class antibiotics against multi-drug resistant Acinetobacter baumannii.

Main Methods:

  • In vitro susceptibility testing of multi-drug resistant Acinetobacter baumannii strains to PBT2 combined with tetracycline, doxycycline, or tigecycline.
  • Murine model of pulmonary infection to assess the in vivo efficacy of PBT2 and tetracycline or tigecycline combinations.

Main Results:

  • In vitro, PBT2 in combination with zinc and tetracyclines demonstrated bactericidal activity against multi-drug resistant Acinetobacter baumannii.
  • Emergence of resistance to the combination therapy imposed a fitness cost on the bacteria.
  • In vivo, PBT2 combined with tetracycline or tigecycline was efficacious in a murine model of Acinetobacter baumannii pulmonary infection.

Conclusions:

  • PBT2 can overcome Acinetobacter baumannii resistance to tetracycline-class antibiotics.
  • PBT2 holds potential as a therapeutic agent to restore the effectiveness of commonly used antibiotics against challenging Acinetobacter baumannii infections.
Keywords:
Acinetobacter baumanniiPBT2antimicrobial resistanceionophoretetracyclines

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