The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries

Liese Van Gompel*, Roosmarijn E C Luiken, Steven Sarrazin, Patrick Munk, Berith Elkær Knudsen, Rasmus B Hansen, Alex Bossers, Frank Møller Aarestrup, Jeroen Dewulf, Jaap A Wagenaar, Dik J Mevius, Heike Schmitt, Dick J J Heederik, Alejandro Dorado-García, Lidwien A M Smit, EFFORT consortium

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Previous studies in food-producing animals have shown associations between antimicrobial use (AMU) and resistance (AMR) in specifically isolated bacterial species. Multi-country data are scarce and only describe between-country differences. Here we investigate associations between the pig faecal mobile resistome and characteristics at the farm-level across Europe. A cross-sectional study was conducted among 176 conventional pig farms from nine European countries. Twenty-five faecal samples from fattening pigs were pooled per farm and acquired resistomes were determined using shotgun metagenomics and the Resfinder reference database, i.e. the full collection of horizontally acquired AMR genes (ARGs). Normalized fragments resistance genes per kilobase reference per million bacterial fragments (FPKM) were calculated. Specific farm-level data (AMU, biosecurity) were collected. Random-effects meta-analyses were performed by country, relating farm-level data to relative ARG abundances (FPKM). Total AMU during fattening was positively associated with total ARG (total FPKM). Positive associations were particularly observed between widely used macrolides and tetracyclines, and ARGs corresponding to the respective antimicrobial classes. Significant AMU-ARG associations were not found for β-lactams and only few colistin ARGs were found, despite high use of these antimicrobial classes in younger pigs. Increased internal biosecurity was directly related to higher abundances of ARGs mainly encoding macrolide resistance. These effects of biosecurity were independent of AMU in mutually adjusted models. Using resistome data in association studies is unprecedented and adds accuracy and new insights to previously observed AMU-AMR associations. Major components of the pig resistome are positively and independently associated with on-farm AMU and biosecurity conditions.
Original languageEnglish
JournalJournal of Antimicrobial Chemotherapy
Volume74
Issue number4
Pages (from-to)865-876
ISSN0305-7453
DOIs
Publication statusPublished - 2019

Cite this

Van Gompel, Liese ; Luiken, Roosmarijn E C ; Sarrazin, Steven ; Munk, Patrick ; Knudsen, Berith Elkær ; Hansen, Rasmus B ; Bossers, Alex ; Aarestrup, Frank Møller ; Dewulf, Jeroen ; Wagenaar, Jaap A ; Mevius, Dik J ; Schmitt, Heike ; Heederik, Dick J J ; Dorado-García, Alejandro ; Smit, Lidwien A M ; consortium, EFFORT. / The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries. In: Journal of Antimicrobial Chemotherapy. 2019 ; Vol. 74, No. 4. pp. 865-876.
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title = "The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries",
abstract = "Previous studies in food-producing animals have shown associations between antimicrobial use (AMU) and resistance (AMR) in specifically isolated bacterial species. Multi-country data are scarce and only describe between-country differences. Here we investigate associations between the pig faecal mobile resistome and characteristics at the farm-level across Europe. A cross-sectional study was conducted among 176 conventional pig farms from nine European countries. Twenty-five faecal samples from fattening pigs were pooled per farm and acquired resistomes were determined using shotgun metagenomics and the Resfinder reference database, i.e. the full collection of horizontally acquired AMR genes (ARGs). Normalized fragments resistance genes per kilobase reference per million bacterial fragments (FPKM) were calculated. Specific farm-level data (AMU, biosecurity) were collected. Random-effects meta-analyses were performed by country, relating farm-level data to relative ARG abundances (FPKM). Total AMU during fattening was positively associated with total ARG (total FPKM). Positive associations were particularly observed between widely used macrolides and tetracyclines, and ARGs corresponding to the respective antimicrobial classes. Significant AMU-ARG associations were not found for β-lactams and only few colistin ARGs were found, despite high use of these antimicrobial classes in younger pigs. Increased internal biosecurity was directly related to higher abundances of ARGs mainly encoding macrolide resistance. These effects of biosecurity were independent of AMU in mutually adjusted models. Using resistome data in association studies is unprecedented and adds accuracy and new insights to previously observed AMU-AMR associations. Major components of the pig resistome are positively and independently associated with on-farm AMU and biosecurity conditions.",
author = "{Van Gompel}, Liese and Luiken, {Roosmarijn E C} and Steven Sarrazin and Patrick Munk and Knudsen, {Berith Elk{\ae}r} and Hansen, {Rasmus B} and Alex Bossers and Aarestrup, {Frank M{\o}ller} and Jeroen Dewulf and Wagenaar, {Jaap A} and Mevius, {Dik J} and Heike Schmitt and Heederik, {Dick J J} and Alejandro Dorado-Garc{\'i}a and Smit, {Lidwien A M} and EFFORT consortium",
year = "2019",
doi = "10.1093/jac/dky518",
language = "English",
volume = "74",
pages = "865--876",
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Van Gompel, L, Luiken, REC, Sarrazin, S, Munk, P, Knudsen, BE, Hansen, RB, Bossers, A, Aarestrup, FM, Dewulf, J, Wagenaar, JA, Mevius, DJ, Schmitt, H, Heederik, DJJ, Dorado-García, A, Smit, LAM & consortium, EFFORT 2019, 'The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries', Journal of Antimicrobial Chemotherapy, vol. 74, no. 4, pp. 865-876. https://doi.org/10.1093/jac/dky518

The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries. / Van Gompel, Liese; Luiken, Roosmarijn E C; Sarrazin, Steven; Munk, Patrick; Knudsen, Berith Elkær; Hansen, Rasmus B; Bossers, Alex; Aarestrup, Frank Møller; Dewulf, Jeroen; Wagenaar, Jaap A; Mevius, Dik J; Schmitt, Heike; Heederik, Dick J J; Dorado-García, Alejandro; Smit, Lidwien A M; consortium, EFFORT.

In: Journal of Antimicrobial Chemotherapy, Vol. 74, No. 4, 2019, p. 865-876.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - The antimicrobial resistome in relation to antimicrobial use and biosecurity in pig farming, a metagenome-wide association study in nine European countries

AU - Van Gompel, Liese

AU - Luiken, Roosmarijn E C

AU - Sarrazin, Steven

AU - Munk, Patrick

AU - Knudsen, Berith Elkær

AU - Hansen, Rasmus B

AU - Bossers, Alex

AU - Aarestrup, Frank Møller

AU - Dewulf, Jeroen

AU - Wagenaar, Jaap A

AU - Mevius, Dik J

AU - Schmitt, Heike

AU - Heederik, Dick J J

AU - Dorado-García, Alejandro

AU - Smit, Lidwien A M

AU - consortium, EFFORT

PY - 2019

Y1 - 2019

N2 - Previous studies in food-producing animals have shown associations between antimicrobial use (AMU) and resistance (AMR) in specifically isolated bacterial species. Multi-country data are scarce and only describe between-country differences. Here we investigate associations between the pig faecal mobile resistome and characteristics at the farm-level across Europe. A cross-sectional study was conducted among 176 conventional pig farms from nine European countries. Twenty-five faecal samples from fattening pigs were pooled per farm and acquired resistomes were determined using shotgun metagenomics and the Resfinder reference database, i.e. the full collection of horizontally acquired AMR genes (ARGs). Normalized fragments resistance genes per kilobase reference per million bacterial fragments (FPKM) were calculated. Specific farm-level data (AMU, biosecurity) were collected. Random-effects meta-analyses were performed by country, relating farm-level data to relative ARG abundances (FPKM). Total AMU during fattening was positively associated with total ARG (total FPKM). Positive associations were particularly observed between widely used macrolides and tetracyclines, and ARGs corresponding to the respective antimicrobial classes. Significant AMU-ARG associations were not found for β-lactams and only few colistin ARGs were found, despite high use of these antimicrobial classes in younger pigs. Increased internal biosecurity was directly related to higher abundances of ARGs mainly encoding macrolide resistance. These effects of biosecurity were independent of AMU in mutually adjusted models. Using resistome data in association studies is unprecedented and adds accuracy and new insights to previously observed AMU-AMR associations. Major components of the pig resistome are positively and independently associated with on-farm AMU and biosecurity conditions.

AB - Previous studies in food-producing animals have shown associations between antimicrobial use (AMU) and resistance (AMR) in specifically isolated bacterial species. Multi-country data are scarce and only describe between-country differences. Here we investigate associations between the pig faecal mobile resistome and characteristics at the farm-level across Europe. A cross-sectional study was conducted among 176 conventional pig farms from nine European countries. Twenty-five faecal samples from fattening pigs were pooled per farm and acquired resistomes were determined using shotgun metagenomics and the Resfinder reference database, i.e. the full collection of horizontally acquired AMR genes (ARGs). Normalized fragments resistance genes per kilobase reference per million bacterial fragments (FPKM) were calculated. Specific farm-level data (AMU, biosecurity) were collected. Random-effects meta-analyses were performed by country, relating farm-level data to relative ARG abundances (FPKM). Total AMU during fattening was positively associated with total ARG (total FPKM). Positive associations were particularly observed between widely used macrolides and tetracyclines, and ARGs corresponding to the respective antimicrobial classes. Significant AMU-ARG associations were not found for β-lactams and only few colistin ARGs were found, despite high use of these antimicrobial classes in younger pigs. Increased internal biosecurity was directly related to higher abundances of ARGs mainly encoding macrolide resistance. These effects of biosecurity were independent of AMU in mutually adjusted models. Using resistome data in association studies is unprecedented and adds accuracy and new insights to previously observed AMU-AMR associations. Major components of the pig resistome are positively and independently associated with on-farm AMU and biosecurity conditions.

U2 - 10.1093/jac/dky518

DO - 10.1093/jac/dky518

M3 - Journal article

VL - 74

SP - 865

EP - 876

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 4

ER -