A novel decoy strategy for polymyxin resistance in acinetobacter baumannii

Jaeeun Park, Misung Kim, Bora Shin, Mingyeong Kang, Jihye Yang, Tae Kwon Lee, Woojun Park

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Article numbere66988
JournaleLife
Volume10
DOIs
Publication statusPublished - 2021 Jun

Bibliographical note

Funding Information:
OMV production is impaired in the absence of PmrB. This finding was supported by our

Funding Information:
We thank the group of Dr. Kwansoo Ko for providing the five clinical isolates from patients at Samsung Medical Center, Sungkyukwan University School of Medicine and thirty-five clinical isolates from the National Culture Collection for Pathogens (NCCP). This work was supported by grants from the National Research Foundation of Korea (No. NRF-2020M3A9H5104237). The funders had no role in study design, data collection or interpretation, or the decision to submit the work for publication.

Publisher Copyright:
© 2021, eLife Sciences Publications Ltd. All rights reserved.

Keywords

  • Acinetobacter baumannii
  • Experimental evolution
  • LPS modifications
  • Outer membrane vesicles
  • Polymyxin resistance
  • Two-component regulatory systems

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology

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