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Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects

View ORCID ProfileJonathan T. L. Kang, View ORCID ProfileJonathan Teo, Denis Bertrand, Amanda Ng, View ORCID ProfileAarthi Ravikrishnan, Melvin Yong, Ng Oon Tek, Kalisvar Marimuthu, Swaine Chen, View ORCID ProfileChng Kern Rei, Gan Yunn-Hwen, Niranjan Nagarajan
doi: https://doi.org/10.1101/2022.05.11.491472
Jonathan T. L. Kang
1Genome Institute of Singapore, Singapore 138672, Singapore
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Jonathan Teo
1Genome Institute of Singapore, Singapore 138672, Singapore
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Denis Bertrand
1Genome Institute of Singapore, Singapore 138672, Singapore
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Amanda Ng
1Genome Institute of Singapore, Singapore 138672, Singapore
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Aarthi Ravikrishnan
1Genome Institute of Singapore, Singapore 138672, Singapore
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Melvin Yong
2Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
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Ng Oon Tek
3Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore 304833, Singapore
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Kalisvar Marimuthu
3Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore 304833, Singapore
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Swaine Chen
1Genome Institute of Singapore, Singapore 138672, Singapore
2Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
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Chng Kern Rei
1Genome Institute of Singapore, Singapore 138672, Singapore
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Gan Yunn-Hwen
2Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
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Niranjan Nagarajan
1Genome Institute of Singapore, Singapore 138672, Singapore
2Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
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  • For correspondence: nagarajann@gis.a-star.edu.sg
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Abstract

Long-term colonization of the gut microbiome by carbapenemase-producing Enterobacteriaceae (CPE) is a growing area of public health concern as it can lead to community transmission and rapid increase in cases of life-threatening CPE infections. Leveraging the observation that many subjects are decolonized without interventions within a year, we used longitudinal shotgun metagenomics (up to 12 timepoints) for detailed characterization of ecological and evolutionary dynamics in the gut microbiome of a cohort of CPE-colonized subjects and family members (n=46; 361 samples). Subjects who underwent decolonization exhibited a distinct ecological shift marked by recovery of microbial diversity, key commensals and anti-inflammatory pathways. In addition, colonization was marked by elevated but unstable Enterobacteriaceae abundances, which exhibited distinct strain-level dynamics for different species (Escherichia coli and Klebsiella pneumoniae). Finally, comparative analysis with whole genome sequencing data from CPE isolates (n=159) helped identify sub-strain variation in key functional genes and the presence of highly similar E. coli and K. pneumoniae strains with variable resistance profiles and plasmid sharing. These results provide an enhanced view into how colonization by multi-drug resistant bacteria associates with altered gut ecology and can enable transfer of resistance genes, even in the absence of overt infection and antibiotic usage.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* Joint First Authors

  • https://github.com/CSB5/CPE-microbiome/

Copyright 
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 May 11, 2022.
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Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects
Jonathan T. L. Kang, Jonathan Teo, Denis Bertrand, Amanda Ng, Aarthi Ravikrishnan, Melvin Yong, Ng Oon Tek, Kalisvar Marimuthu, Swaine Chen, Chng Kern Rei, Gan Yunn-Hwen, Niranjan Nagarajan
bioRxiv 2022.05.11.491472; doi: https://doi.org/10.1101/2022.05.11.491472
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Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects
Jonathan T. L. Kang, Jonathan Teo, Denis Bertrand, Amanda Ng, Aarthi Ravikrishnan, Melvin Yong, Ng Oon Tek, Kalisvar Marimuthu, Swaine Chen, Chng Kern Rei, Gan Yunn-Hwen, Niranjan Nagarajan
bioRxiv 2022.05.11.491472; doi: https://doi.org/10.1101/2022.05.11.491472

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