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In vitro demonstration of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome

View ORCID ProfileSamuel C. Forster, View ORCID ProfileJunyan Liu, View ORCID ProfileNitin Kumar, View ORCID ProfileEmily L. Gulliver, Jodee A. Gould, View ORCID ProfileAlejandra Escobar-Zepeda, Tapoka Mkandawire, Lindsay J. Pike, View ORCID ProfileYan Shao, Mark D. Stares, View ORCID ProfileHilary P. Browne, B. Anne Neville, View ORCID ProfileTrevor D. Lawley
doi: https://doi.org/10.1101/2022.01.18.476738
Samuel C. Forster
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
2Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, 3168, Australia
3Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, 3800, Australia
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  • ORCID record for Samuel C. Forster
  • For correspondence: sf15@sanger.ac.uk tl2@sanger.ac.uk
Junyan Liu
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
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Nitin Kumar
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
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Emily L. Gulliver
2Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, 3168, Australia
3Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, 3800, Australia
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Jodee A. Gould
2Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, 3168, Australia
3Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, 3800, Australia
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Alejandra Escobar-Zepeda
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
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  • ORCID record for Alejandra Escobar-Zepeda
Tapoka Mkandawire
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
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Lindsay J. Pike
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
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Yan Shao
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
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  • ORCID record for Yan Shao
Mark D. Stares
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
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Hilary P. Browne
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
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B. Anne Neville
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
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Trevor D. Lawley
1Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK
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  • ORCID record for Trevor D. Lawley
  • For correspondence: sf15@sanger.ac.uk tl2@sanger.ac.uk
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Abstract

Mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) disseminate ARGs when they mobilise into new bacterial hosts. To investigate the scale of such horizontal gene transfer (HGT) events between human gut commensals and enteropathogens for the first time, we compared 1354 cultured commensal strains (540 species) to 45,403 enteropathogen strains (12 species) and found 64,188 MGE-mediated ARG transfer events between the two groups using established methods. Among the 5931 MGEs involved, we found 15 broad host range elements predicted to have crossed different bacterial phyla while also occurring in animal and environmental microbiomes. We experimentally demonstrated that predicted broad host range MGEs can mobilise from commensals Dorea longicatena and Hungatella hathewayi to enteropathogens Klebsiella oxytoca, crossing phyla simultaneously. Our work establishes the MGE-mediated ARG dissemination network between human gut commensals and enteropathogens and highlights novel broad host range MGEs as targets for future ARG dissemination management.

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-NC-ND 4.0 International license.
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Posted January 18, 2022.
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In vitro demonstration of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome
Samuel C. Forster, Junyan Liu, Nitin Kumar, Emily L. Gulliver, Jodee A. Gould, Alejandra Escobar-Zepeda, Tapoka Mkandawire, Lindsay J. Pike, Yan Shao, Mark D. Stares, Hilary P. Browne, B. Anne Neville, Trevor D. Lawley
bioRxiv 2022.01.18.476738; doi: https://doi.org/10.1101/2022.01.18.476738
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In vitro demonstration of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome
Samuel C. Forster, Junyan Liu, Nitin Kumar, Emily L. Gulliver, Jodee A. Gould, Alejandra Escobar-Zepeda, Tapoka Mkandawire, Lindsay J. Pike, Yan Shao, Mark D. Stares, Hilary P. Browne, B. Anne Neville, Trevor D. Lawley
bioRxiv 2022.01.18.476738; doi: https://doi.org/10.1101/2022.01.18.476738

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