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.

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.

Metrics

  • 4,166
    views
  • 552
    downloads
  • 30
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

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

Further reading

    1. Cell Biology
    2. Microbiology and Infectious Disease
    Clément Mazeaud, Stefan Pfister ... Laurent Chatel-Chaix
    Research Article

    Zika virus (ZIKV) infection causes significant human disease that, with no approved treatment or vaccine, constitutes a major public health concern. Its life cycle entirely relies on the cytoplasmic fate of the viral RNA genome (vRNA) through a fine-tuned equilibrium between vRNA translation, replication, and packaging into new virions, all within virus-induced replication organelles (vROs). In this study, with an RNA interference (RNAi) mini-screening and subsequent functional characterization, we have identified insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) as a new host dependency factor that regulates vRNA synthesis. In infected cells, IGF2BP2 associates with viral NS5 polymerase and redistributes to the perinuclear viral replication compartment. Combined fluorescence in situ hybridization-based confocal imaging, in vitro binding assays, and immunoprecipitation coupled to RT-qPCR showed that IGF2BP2 directly interacts with ZIKV vRNA 3’ nontranslated region. Using ZIKV sub-genomic replicons and a replication-independent vRO induction system, we demonstrated that IGF2BP2 knockdown impairs de novo vRO biogenesis and, consistently, vRNA synthesis. Finally, the analysis of immunopurified IGF2BP2 complex using quantitative mass spectrometry and RT-qPCR revealed that ZIKV infection alters the protein and RNA interactomes of IGF2BP2. Altogether, our data support that ZIKV hijacks and remodels the IGF2BP2 ribonucleoprotein complex to regulate vRO biogenesis and vRNA neosynthesis.

    1. Microbiology and Infectious Disease
    Linkang Wang, Haiyan Wang ... Ping Qian
    Research Article

    Bacillus velezensis is a species of Bacillus that has been widely investigated because of its broad-spectrum antimicrobial activity. However, most studies on B. velezensis have focused on the biocontrol of plant diseases, with few reports on antagonizing Salmonella Typhimurium infections. In this investigation, it was discovered that B. velezensis HBXN2020, which was isolated from healthy black pigs, possessed strong anti-stress and broad-spectrum antibacterial activity. Importantly, B. velezensis HBXN2020 did not cause any adverse side effects in mice when administered at various doses (1×107, 1×108, and 1×109 CFU) for 14 days. Supplementing B. velezensis HBXN2020 spores, either as a curative or preventive measure, dramatically reduced the levels of S. Typhimurium ATCC14028 in the mice’s feces, ileum, cecum, and colon, as well as the disease activity index (DAI), in a model of infection caused by this pathogen in mice. Additionally, supplementing B. velezensis HBXN2020 spores significantly regulated cytokine levels (Tnfa, Il1b, Il6, and Il10) and maintained the expression of tight junction proteins and mucin protein. Most importantly, adding B. velezensis HBXN2020 spores to the colonic microbiota improved its stability and increased the amount of beneficial bacteria (Lactobacillus and Akkermansia). All together, B. velezensis HBXN2020 can improve intestinal microbiota stability and barrier integrity and reduce inflammation to help treat infection by S. Typhimurium.