Mobilome-driven segregation of the resistome in biological wastewater treatment

  1. Laura de Nies
  2. Susheel Bhanu Busi
  3. Benoit Josef Kunath
  4. Patrick May
  5. Paul Wilmes  Is a corresponding author
  1. University of Luxembourg, Luxembourg

Abstract

Biological wastewater treatment plants (BWWTP) are considered to be hotspots of evolution and subsequent spread of antimicrobial resistance (AMR). Mobile genetic elements (MGEs) promote the mobilization and dissemination of antimicrobial resistance genes (ARGs) and are thereby critical mediators of AMR within the BWWTP microbial community. At present, it is unclear whether specific AMR categories are differentially disseminated via bacteriophages (phages) or plasmids. To understand the segregation of AMR in relation to MGEs, we analyzed meta-omic (metagenomic, metatranscriptomic and metaproteomic) data systematically collected over 1.5 years from a BWWTP. Our results showed a core group of fifteen AMR categories which were found across all timepoints. Some of these AMR categories were disseminated exclusively (bacitracin) or primarily (aminoglycoside, MLS and sulfonamide) via plasmids or phages (fosfomycin and peptide), whereas others were disseminated equally by both MGEs. Combined and timepoint-specific analyses of gene, transcript and protein abundances further demonstrated that aminoglycoside, bacitracin and sulfonamide resistance genes were expressed more by plasmids, in contrast to fosfomycin and peptide AMR expression by phages, thereby validating our genomic findings. In the analyzed communities, the dominant taxon Candidatus Microthrix parvicella was a major contributor to several AMR categories whereby its plasmids primarily mediated aminoglycoside resistance. Importantly, we also found AMR associated with ESKAPEE pathogens within the BWWTP, for which MGEs also contributed differentially to the dissemination of ARGs. Collectively our findings pave the way towards understanding the segmentation of AMR within MGEs, thereby shedding new light on resistome populations and their mediators, essential elements that are of immediate relevance to human health.

Data availability

The genomic FASTQ files used in this work (previously published) are publicly available at NCBI BioProject PRJNA230567. Metaproteomic data (previously published) are publicly available at the PRIDE database under accession number PXD013655.The open-source tools and algorithms used for the data analyses are reported in the Methods section, including relevant flags used for the various tools. Additionally, custom code for further analysis and generation of the figures can be found at: https://git-r3lab.uni.lu/laura.denies/lao_scripts

The following previously published data sets were used

Article and author information

Author details

  1. Laura de Nies

    Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
    Competing interests
    The authors declare that no competing interests exist.
  2. Susheel Bhanu Busi

    Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7559-3400
  3. Benoit Josef Kunath

    Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3356-8562
  4. Patrick May

    Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8698-3770
  5. Paul Wilmes

    Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
    For correspondence
    paul.wilmes@uni.lu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6478-2924

Funding

Fonds National de la Recherche Luxembourg (CORE/BM/11333923)

  • Paul Wilmes

European Research Council (ERC-CoG 863664)

  • Paul Wilmes

Fonds National de la Recherche Luxembourg (PRIDE/11823097)

  • Paul Wilmes

Fonds National de la Recherche Luxembourg (PRIDE/11823097)

  • Laura de Nies

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CRSII5_180241)

  • Susheel Bhanu Busi

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

Publication history

  1. Preprint posted: November 15, 2021 (view preprint)
  2. Received: June 19, 2022
  3. Accepted: September 15, 2022
  4. Accepted Manuscript published: September 16, 2022 (version 1)

Copyright

© 2022, de Nies 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. Laura de Nies
  2. Susheel Bhanu Busi
  3. Benoit Josef Kunath
  4. Patrick May
  5. Paul Wilmes
(2022)
Mobilome-driven segregation of the resistome in biological wastewater treatment
eLife 11:e81196.
https://doi.org/10.7554/eLife.81196
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