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Mobilome-driven segregation of the resistome in biological wastewater treatment

View ORCID ProfileLaura de Nies, View ORCID ProfileSusheel Bhanu Busi, Benoit Josef Kunath, View ORCID ProfilePatrick May, Paul Wilmes
doi: https://doi.org/10.1101/2021.11.15.468621
Laura de Nies
1Luxembourg Centre for Systems Biomedicine, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette, L-4362, Luxembourg
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Susheel Bhanu Busi
1Luxembourg Centre for Systems Biomedicine, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette, L-4362, Luxembourg
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Benoit Josef Kunath
1Luxembourg Centre for Systems Biomedicine, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette, L-4362, Luxembourg
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Patrick May
1Luxembourg Centre for Systems Biomedicine, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette, L-4362, Luxembourg
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Paul Wilmes
1Luxembourg Centre for Systems Biomedicine, 7, avenue des Hauts-Fourneaux, Esch-sur-Alzette, L-4362, Luxembourg
2Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, 6, avenue du Swing, Belvaux, L-4367, Luxembourg
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  • For correspondence: paul.wilmes@uni.lu
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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, sulfonamide) via plasmids or phages (fosfomycin and peptide), whereas others were disseminated equally by both MGEs. Subsequent expression- and protein-level analyses 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. Longitudinal assessment further underlined these findings whereby the log2-fold changes of aminoglycoside, bacitracin and sulfonamide resistance genes were increased in plasmids, while fosfomycin and peptide resistance showed similar trends in phages. 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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted November 15, 2021.
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Mobilome-driven segregation of the resistome in biological wastewater treatment
Laura de Nies, Susheel Bhanu Busi, Benoit Josef Kunath, Patrick May, Paul Wilmes
bioRxiv 2021.11.15.468621; doi: https://doi.org/10.1101/2021.11.15.468621
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Mobilome-driven segregation of the resistome in biological wastewater treatment
Laura de Nies, Susheel Bhanu Busi, Benoit Josef Kunath, Patrick May, Paul Wilmes
bioRxiv 2021.11.15.468621; doi: https://doi.org/10.1101/2021.11.15.468621

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