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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
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.
Abstract:
Modification of the outer membrane charge by a polymyxin B (PMB)-induced PmrAB two-component system appears to be a dominant phenomenon in PMB-resistant Acinetobacter baumannii. PMB-resistant variants and many clinical isolates also appeared to produce outer membrane vesicles (OMVs). Genomic, transcriptomic, and proteomic analyses revealed that upregulation of the pmr operon and decreased membrane-linkage proteins (OmpA, OmpW, and BamE) are linked to overproduction of OMVs, which also promoted enhanced biofilm formation. The addition of OMVs from PMB-resistant variants into the cultures of PMB-susceptible A. baumannii and the clinical isolates protected these susceptible bacteria from PMB. Taxonomic profiling of in vitro human gut microbiomes under anaerobic conditions demonstrated that OMVs completely protected the microbial community against PMB treatment. A Galleria mellonella-infection model with PMB treatment showed that OMVs increased the mortality rate of larvae by protecting A. baumannii from PMB. Taken together, OMVs released from A. baumannii functioned as decoys against PMB.
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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