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Resistance to Metals Used in Agricultural Production

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  • Authors: Christopher Rensing1, Arshnee Moodley2, Lina M. Cavaco3, Sylvia Franke McDevitt4
  • Editors: Frank Møller Aarestrup5, Stefan Schwarz6, Jianzhong Shen7, Lina Cavaco8
    Affiliations: 1: Institute of Environmental Microbiology, College of Resource and Environment, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; 2: Veterinary Clinical Microbiology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark; 3: Department for Bacteria, Parasites, and Fungi, Infectious Disease Preparedness, Statens Serum Institut and Faculty of Health and Medical Sciences, University of Copenhagen, 2300 Copenhagen, Denmark; 4: Biology, Skidmore College, Saratoga Springs, NY 12866; 5: Technical University of Denmark, Lyngby, Denmark; 6: Freie Universität Berlin, Berlin, Germany; 7: China Agricultural University, Beijing, China; 8: Statens Serum Institute, University of Copenhagen, Copenhagen, Denmark
  • Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0025-2017
  • Received 10 January 2018 Accepted 21 February 2018 Published 19 April 2018
  • Christopher Rensing, [email protected]
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  • Abstract:

    Metals and metalloids have been used alongside antibiotics in livestock production for a long time. The potential and acute negative impact on the environment and human health of these livestock feed supplements has prompted lawmakers to ban or discourage the use of some or all of these supplements. This article provides an overview of current use in the European Union and the United States, detected metal resistance determinants, and the proteins and mechanisms responsible for conferring copper and zinc resistance in bacteria. A detailed description of the most common copper and zinc metal resistance determinants is given to illustrate not only the potential danger of coselecting antibiotic resistance genes but also the potential to generate bacterial strains with an increased potential to be pathogenic to humans. For example, the presence of a 20-gene copper pathogenicity island is highlighted since bacteria containing this gene cluster could be readily isolated from copper-fed pigs, and many pathogenic strains, including O104:H4, contain this potential virulence factor, suggesting a potential link between copper supplements in livestock and the evolution of pathogens.

  • Citation: Rensing C, Moodley A, Cavaco L, McDevitt S. 2018. Resistance to Metals Used in Agricultural Production. Microbiol Spectrum 6(2):ARBA-0025-2017. doi:10.1128/microbiolspec.ARBA-0025-2017.


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Metals and metalloids have been used alongside antibiotics in livestock production for a long time. The potential and acute negative impact on the environment and human health of these livestock feed supplements has prompted lawmakers to ban or discourage the use of some or all of these supplements. This article provides an overview of current use in the European Union and the United States, detected metal resistance determinants, and the proteins and mechanisms responsible for conferring copper and zinc resistance in bacteria. A detailed description of the most common copper and zinc metal resistance determinants is given to illustrate not only the potential danger of coselecting antibiotic resistance genes but also the potential to generate bacterial strains with an increased potential to be pathogenic to humans. For example, the presence of a 20-gene copper pathogenicity island is highlighted since bacteria containing this gene cluster could be readily isolated from copper-fed pigs, and many pathogenic strains, including O104:H4, contain this potential virulence factor, suggesting a potential link between copper supplements in livestock and the evolution of pathogens.

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Copper fitness (or pathogenicity) island in . Genes and protein products of the enterobacterial copper fitness island composed of the - and -determinants. The genes, including their transcriptional/translational direction, are indicated below the illustration of the proposed or experimentally determined function of the proteins encoded by the system. Refer to text for details. (Reprinted with permission [ 171 ].)

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0025-2017
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Copper fitness island in . Genes and proposed protein products of the copper island in HF50105 (GenBank accession number AITS01000024). The genes, including their transcriptional/translational direction, are indicated below the illustration of the proposed function of the proteins. (Refer to text for details.) Adjacent to and separating the genes involved in copper resistance are genes encoding prolipoprotein diacylglyceryl transferase (A), integral membrane protein (B), predicted metal-binding protein/chaperone (C), hypothetical protein (H), transposase (T), and disrupted P-type ATPase (F) that have been identified. (Reprinted with permission [ 171 ].)

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0025-2017
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New proposed maximum limits of copper in complete animal feed

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0025-2017
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New proposed maximum limits of zinc in complete feed

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0025-2017
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Bacteria of animal origin for which copper and zinc resistance has been described

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0025-2017
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Copper- and zinc-resistance genes identified in bacteria from livestock

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0025-2017
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Distribution of and yersiniabactin biosynthesis genes among

Source: microbiolspec April 2018 vol. 6 no. 2 doi:10.1128/microbiolspec.ARBA-0025-2017

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