A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii

Jaeeun Park1, Misung Kim1, Bora Shin1

  • 1Laboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of Korea.

Elife
|June 28, 2021
PubMed

Insights

Outer membrane vesicles (OMVs) from polymyxin B-resistant Acinetobacter baumannii protect bacteria and gut microbes from the antibiotic. These OMVs act as decoys, sequestering the drug and enhancing bacterial survival.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Antimicrobial Resistance

Background:

  • Polymyxin B (PMB) resistance in Acinetobacter baumannii is often linked to outer membrane modifications.
  • Outer membrane vesicles (OMVs) are increasingly recognized for their role in bacterial adaptation and virulence.

Purpose of the Study:

  • To investigate the role of OMVs in PMB resistance in Acinetobacter baumannii.
  • To determine if OMVs can protect bacteria and microbial communities from PMB treatment.

Main Methods:

  • Genomic, transcriptomic, and proteomic analyses of PMB-resistant A. baumannii.
  • Assessment of OMV production and its link to pmr operon upregulation and membrane protein levels.
  • In vitro studies using human gut microbiomes and an in vivo Galleria mellonella infection model to evaluate OMV-mediated protection against PMB.

Main Results:

  • PMB resistance in A. baumannii is associated with increased OMV production, linked to pmr operon upregulation and decreased membrane-linker proteins.
  • OMVs from resistant strains protected both susceptible A. baumannii and diverse gut microbial communities from PMB.
  • OMVs enhanced biofilm formation and increased larval mortality in a Galleria mellonella model by shielding bacteria from PMB.

Conclusions:

  • OMVs produced by PMB-resistant A. baumannii act as decoys, effectively neutralizing PMB.
  • OMV-mediated protection extends to both the target pathogen and the commensal gut microbiota, highlighting a novel resistance mechanism.

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