A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii

  1. Jaeeun Park
  2. Misung Kim
  3. Bora Shin
  4. Mingyeong Kang
  5. Jihye Yang
  6. Tae Kwon Lee
  7. Woojun Park  Is a corresponding author
  1. Korea University, Republic of Korea
  2. Yonsei University, 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.

Data availability

1. Sequence reads for the experimentally evolved isolates are accessible from the NCBI sequence archives under accession numbers PRJNA530195 (Lab-WT), PRJNA530197 (PMRLow), and PRJNA530202 (PMRHigh).2. The RNA-seq data have been deposited in NCBI under Gene Expression Omnibus (GEO) accession number GSE163581.3. The bacterial community data have been deposited in NCBI under Sequence Read Archive (SRA) accession number SRX9819399 PRJNA689940, SRX9819397 PRJNA689944 and SRX9819398 PRJNA689944.

The following data sets were generated
    1. Kim M
    (2021) PMB
    NCBI Bioproject ID SRX9819397 PRJNA689944.
    1. Kim M
    (2021) OMV->PMB.
    NCBI Bioproject ID SRX9819398 PRJNA689944.

Article and author information

Author details

  1. Jaeeun Park

    Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  2. Misung Kim

    Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  3. Bora Shin

    Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  4. Mingyeong Kang

    Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  5. Jihye Yang

    Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  6. Tae Kwon Lee

    Environmental Engineering, Yonsei University, Wonju, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3845-7316
  7. Woojun Park

    Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of Korea
    For correspondence
    wpark@korea.ac.kr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3166-1528

Funding

National Research Foundation of Korea (NRF-2020M3A9H5104237)

  • Woojun Park

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. María Mercedes Zambrano, CorpoGen, Colombia

Version history

  1. Received: January 28, 2021
  2. Accepted: June 27, 2021
  3. Accepted Manuscript published: June 28, 2021 (version 1)
  4. Version of Record published: July 30, 2021 (version 2)

Copyright

© 2021, Park et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jaeeun Park
  2. Misung Kim
  3. Bora Shin
  4. Mingyeong Kang
  5. Jihye Yang
  6. Tae Kwon Lee
  7. Woojun Park
(2021)
A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii
eLife 10:e66988.
https://doi.org/10.7554/eLife.66988

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https://doi.org/10.7554/eLife.66988

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