Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers

Alaric W. D’Souza; Manish Boolchandani; COMBAT Consortium; Sanket Patel; Gianluca Galazzo; Jarne M. van Hattem; Maris S. Arcilla; Damian C. Melles; Menno D. de Jong; Constance Schultsz; Gautam Dantas; John Penders

doi:10.1186/s13073-021-00893-z

Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers

Alaric W. D’Souza, Manish Boolchandani, COMBAT Consortium, Sanket Patel, Gianluca Galazzo, Jarne M. van Hattem, Maris S. Arcilla, Damian C. Melles, Menno D. de Jong, Constance Schultsz, Gautam Dantas^*, John Penders^*

^*Corresponding author for this work

Medical Microbiology & Infectious Diseases

Research output: Contribution to journal › Article › Academic › peer-review

25 Citations (Scopus)

Abstract

Background: Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel’s effects on the gut resistome remain largely unknown. Methods: Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of 190 Dutch individuals, before and after travel to diverse international locations. Results: Travel markedly increased the abundance and α-diversity of AMR genes in the travelers’ gut resistome, and we determined that 56 unique AMR genes showed significant acquisition following international travel. These acquisition events were biased towards AMR genes with efflux, inactivation, and target replacement resistance mechanisms. Travel-induced shaping of the gut resistome had distinct correlations with geographical destination, so individuals returning to The Netherlands from the same destination country were more likely to have similar resistome features. Finally, we identified and detailed specific acquisition events of high-risk, mobile genetic element-associated AMR genes including qnr fluoroquinolone resistance genes, bla_CTX-M family extended-spectrum β-lactamases, and the plasmid-borne mcr-1 colistin resistance gene. Conclusions: Our results show that travel shapes the architecture of the human gut resistome and results in AMR gene acquisition against a variety of antimicrobial drug classes. These broad acquisitions highlight the putative risks that international travel poses to public health by gut resistome perturbation and the global spread of locally endemic AMR genes.

Original language	English
Article number	79
Journal	Genome Medicine
Volume	13
Issue number	1
DOIs	https://doi.org/10.1186/s13073-021-00893-z
Publication status	Published - 7 Jun 2021

Bibliographical note

Funding Information:
The COMBAT study was funded by The Netherlands Organization for Health, Research and Development (ZonMw; 50-51700-98-120). This work was supported in part by awards to JP through the Dutch Research Council (VIDI grant 016.156.427) and GD through the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R01AI123394), the Congressionally Directed Medical Research Program of the US Department of Defense (W81XWH1810225), and the Edward Mallinckrodt, Jr. Foundation (Scholar Award). AWD received support from the Institutional Program Unifying Population and Laboratory-Based Sciences Burroughs Welcome Fund grant to Washington University and the National Research Service Award-Medical Scientist grant to Washington University (T32 GM007200). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Publisher Copyright:
© 2021, The Author(s).

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D’Souza, A. W., Boolchandani, M., COMBAT Consortium, Patel, S., Galazzo, G., van Hattem, J. M., Arcilla, M. S., Melles, D. C., de Jong, M. D., Schultsz, C., Dantas, G., & Penders, J. (2021). Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers. Genome Medicine, 13(1), Article 79. https://doi.org/10.1186/s13073-021-00893-z

@article{d48ae0c4c96a4a16a99816f691a86646,

title = "Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers",

abstract = "Background: Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel{\textquoteright}s effects on the gut resistome remain largely unknown. Methods: Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of 190 Dutch individuals, before and after travel to diverse international locations. Results: Travel markedly increased the abundance and α-diversity of AMR genes in the travelers{\textquoteright} gut resistome, and we determined that 56 unique AMR genes showed significant acquisition following international travel. These acquisition events were biased towards AMR genes with efflux, inactivation, and target replacement resistance mechanisms. Travel-induced shaping of the gut resistome had distinct correlations with geographical destination, so individuals returning to The Netherlands from the same destination country were more likely to have similar resistome features. Finally, we identified and detailed specific acquisition events of high-risk, mobile genetic element-associated AMR genes including qnr fluoroquinolone resistance genes, blaCTX-M family extended-spectrum β-lactamases, and the plasmid-borne mcr-1 colistin resistance gene. Conclusions: Our results show that travel shapes the architecture of the human gut resistome and results in AMR gene acquisition against a variety of antimicrobial drug classes. These broad acquisitions highlight the putative risks that international travel poses to public health by gut resistome perturbation and the global spread of locally endemic AMR genes.",

author = "D{\textquoteright}Souza, {Alaric W.} and Manish Boolchandani and {COMBAT Consortium} and Sanket Patel and Gianluca Galazzo and {van Hattem}, {Jarne M.} and Arcilla, {Maris S.} and Melles, {Damian C.} and {de Jong}, {Menno D.} and Constance Schultsz and {van Genderen}, {Perry J.} and Verbrugh, {Henri A.} and Gautam Dantas and John Penders",

note = "Funding Information: The COMBAT study was funded by The Netherlands Organization for Health, Research and Development (ZonMw; 50-51700-98-120). This work was supported in part by awards to JP through the Dutch Research Council (VIDI grant 016.156.427) and GD through the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R01AI123394), the Congressionally Directed Medical Research Program of the US Department of Defense (W81XWH1810225), and the Edward Mallinckrodt, Jr. Foundation (Scholar Award). AWD received support from the Institutional Program Unifying Population and Laboratory-Based Sciences Burroughs Welcome Fund grant to Washington University and the National Research Service Award-Medical Scientist grant to Washington University (T32 GM007200). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = jun,

day = "7",

doi = "10.1186/s13073-021-00893-z",

language = "English",

volume = "13",

journal = "Genome Medicine",

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D’Souza, AW, Boolchandani, M, COMBAT Consortium, Patel, S, Galazzo, G, van Hattem, JM, Arcilla, MS, Melles, DC, de Jong, MD, Schultsz, C, Dantas, G & Penders, J 2021, 'Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers', Genome Medicine, vol. 13, no. 1, 79. https://doi.org/10.1186/s13073-021-00893-z

TY - JOUR

T1 - Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers

AU - D’Souza, Alaric W.

AU - Boolchandani, Manish

AU - COMBAT Consortium

AU - Patel, Sanket

AU - Galazzo, Gianluca

AU - van Hattem, Jarne M.

AU - Arcilla, Maris S.

AU - Melles, Damian C.

AU - de Jong, Menno D.

AU - Schultsz, Constance

AU - van Genderen, Perry J.

AU - Verbrugh, Henri A.

AU - Dantas, Gautam

AU - Penders, John

N1 - Funding Information: The COMBAT study was funded by The Netherlands Organization for Health, Research and Development (ZonMw; 50-51700-98-120). This work was supported in part by awards to JP through the Dutch Research Council (VIDI grant 016.156.427) and GD through the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R01AI123394), the Congressionally Directed Medical Research Program of the US Department of Defense (W81XWH1810225), and the Edward Mallinckrodt, Jr. Foundation (Scholar Award). AWD received support from the Institutional Program Unifying Population and Laboratory-Based Sciences Burroughs Welcome Fund grant to Washington University and the National Research Service Award-Medical Scientist grant to Washington University (T32 GM007200). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. Publisher Copyright: © 2021, The Author(s).

PY - 2021/6/7

Y1 - 2021/6/7

N2 - Background: Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel’s effects on the gut resistome remain largely unknown. Methods: Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of 190 Dutch individuals, before and after travel to diverse international locations. Results: Travel markedly increased the abundance and α-diversity of AMR genes in the travelers’ gut resistome, and we determined that 56 unique AMR genes showed significant acquisition following international travel. These acquisition events were biased towards AMR genes with efflux, inactivation, and target replacement resistance mechanisms. Travel-induced shaping of the gut resistome had distinct correlations with geographical destination, so individuals returning to The Netherlands from the same destination country were more likely to have similar resistome features. Finally, we identified and detailed specific acquisition events of high-risk, mobile genetic element-associated AMR genes including qnr fluoroquinolone resistance genes, blaCTX-M family extended-spectrum β-lactamases, and the plasmid-borne mcr-1 colistin resistance gene. Conclusions: Our results show that travel shapes the architecture of the human gut resistome and results in AMR gene acquisition against a variety of antimicrobial drug classes. These broad acquisitions highlight the putative risks that international travel poses to public health by gut resistome perturbation and the global spread of locally endemic AMR genes.

AB - Background: Antimicrobial-resistant bacteria and their antimicrobial resistance (AMR) genes can spread by hitchhiking in human guts. International travel can exacerbate this public health threat when travelers acquire AMR genes endemic to their destinations and bring them back to their home countries. Prior studies have demonstrated travel-related acquisition of specific opportunistic pathogens and AMR genes, but the extent and magnitude of travel’s effects on the gut resistome remain largely unknown. Methods: Using whole metagenomic shotgun sequencing, functional metagenomics, and Dirichlet multinomial mixture models, we investigated the abundance, diversity, function, resistome architecture, and context of AMR genes in the fecal microbiomes of 190 Dutch individuals, before and after travel to diverse international locations. Results: Travel markedly increased the abundance and α-diversity of AMR genes in the travelers’ gut resistome, and we determined that 56 unique AMR genes showed significant acquisition following international travel. These acquisition events were biased towards AMR genes with efflux, inactivation, and target replacement resistance mechanisms. Travel-induced shaping of the gut resistome had distinct correlations with geographical destination, so individuals returning to The Netherlands from the same destination country were more likely to have similar resistome features. Finally, we identified and detailed specific acquisition events of high-risk, mobile genetic element-associated AMR genes including qnr fluoroquinolone resistance genes, blaCTX-M family extended-spectrum β-lactamases, and the plasmid-borne mcr-1 colistin resistance gene. Conclusions: Our results show that travel shapes the architecture of the human gut resistome and results in AMR gene acquisition against a variety of antimicrobial drug classes. These broad acquisitions highlight the putative risks that international travel poses to public health by gut resistome perturbation and the global spread of locally endemic AMR genes.

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DO - 10.1186/s13073-021-00893-z

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AN - SCOPUS:85107745423

SN - 1756-994X

VL - 13

JO - Genome Medicine

JF - Genome Medicine

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ER -

Destination shapes antibiotic resistance gene acquisitions, abundance increases, and diversity changes in Dutch travelers

Abstract

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