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Title: Clusters of antibiotic resistance genes enriched together stay together in swine agriculture

Abstract

Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundance of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to themore » use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk.Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance genes if they are genetically linked. No links to bacterial membership were observed for these clusters of resistance genes. These findings urge deeper understanding of colocalization of resistance genes and mobile genetic elements in resistance islands and their distribution throughout antibiotic-exposed microbiomes. In addition, as governments seek to combat the rise in antibiotic resistance, a balance is sought between ensuring proper animal health and welfare and preserving medically important antibiotics for therapeutic use. Metagenomic and genomic monitoring will be critical to determine if resistance genes can be reduced in animal microbiomes, or if these gene clusters will continue to be coselected by antibiotics not deemed medically important for human health but used for growth promotion or by medically important antibiotics used therapeutically.« less

Authors:
 [1];  [2];  [3];  [3];  [2];  [4];  [5];  [6]
  1. Michigan State Univ., East Lansing, Michigan (United States). Center for Microbial Ecology and Dept. of Plant, Soil and Microbial Sciences; U.S. Dept. of Agriculture, Ames, Iowa (United States). Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, Agricultural Research Service
  2. Michigan State Univ., East Lansing, Michigan (United States). Center for Microbial Ecology and Dept. of Civil and Environmental Engineering
  3. Michigan State Univ., East Lansing, Michigan (United States). Center for Microbial Ecology
  4. U.S. Dept. of Agriculture, Ames, Iowa (United States). Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, Agricultural Research Service
  5. Chinese Academy of Sciences, Xiamen (China). Key Lab of Urban Environment and Health, Inst. of Urban Environment; Chinese Academy of Sciences, Beijing (China). Research Center for Eco-environmental Sciences
  6. Michigan State Univ., East Lansing, Michigan (United States). Center for Microbial Ecology and Dept. of Plant, Soil and Microbial Sciences
Publication Date:
Research Org.:
Michigan State Univ., East Lansing, Michigan (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1288311
Grant/Contract Number:  
FG02-99ER62848
Resource Type:
Accepted Manuscript
Journal Name:
mBio (Online)
Additional Journal Information:
Journal Name: mBio (Online); Journal Volume: 7; Journal Issue: 2; Journal ID: ISSN 2150-7511
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; class 1 integrons; real-time pcr; multidrug-resistance; intestinal bacteria; insertion sequences; food animals; soil; cassettes; plasmids; antimicrobials

Citation Formats

Johnson, Timothy A., Stedtfeld, Robert D., Wang, Qiong, Cole, James R., Hashsham, Syed A., Looft, Torey, Zhu, Yong -Guan, and Tiedje, James M. Clusters of antibiotic resistance genes enriched together stay together in swine agriculture. United States: N. p., 2016. Web. https://doi.org/10.1128/mBio.02214-15.
Johnson, Timothy A., Stedtfeld, Robert D., Wang, Qiong, Cole, James R., Hashsham, Syed A., Looft, Torey, Zhu, Yong -Guan, & Tiedje, James M. Clusters of antibiotic resistance genes enriched together stay together in swine agriculture. United States. https://doi.org/10.1128/mBio.02214-15
Johnson, Timothy A., Stedtfeld, Robert D., Wang, Qiong, Cole, James R., Hashsham, Syed A., Looft, Torey, Zhu, Yong -Guan, and Tiedje, James M. Tue . "Clusters of antibiotic resistance genes enriched together stay together in swine agriculture". United States. https://doi.org/10.1128/mBio.02214-15. https://www.osti.gov/servlets/purl/1288311.
@article{osti_1288311,
title = {Clusters of antibiotic resistance genes enriched together stay together in swine agriculture},
author = {Johnson, Timothy A. and Stedtfeld, Robert D. and Wang, Qiong and Cole, James R. and Hashsham, Syed A. and Looft, Torey and Zhu, Yong -Guan and Tiedje, James M.},
abstractNote = {Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundance of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk.Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance genes if they are genetically linked. No links to bacterial membership were observed for these clusters of resistance genes. These findings urge deeper understanding of colocalization of resistance genes and mobile genetic elements in resistance islands and their distribution throughout antibiotic-exposed microbiomes. In addition, as governments seek to combat the rise in antibiotic resistance, a balance is sought between ensuring proper animal health and welfare and preserving medically important antibiotics for therapeutic use. Metagenomic and genomic monitoring will be critical to determine if resistance genes can be reduced in animal microbiomes, or if these gene clusters will continue to be coselected by antibiotics not deemed medically important for human health but used for growth promotion or by medically important antibiotics used therapeutically.},
doi = {10.1128/mBio.02214-15},
journal = {mBio (Online)},
number = 2,
volume = 7,
place = {United States},
year = {2016},
month = {4}
}

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