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      Fecal pollution can explain antibiotic resistance gene abundances in anthropogenically impacted environments

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          Abstract

          Discharge of treated sewage leads to release of antibiotic resistant bacteria, resistance genes and antibiotic residues to the environment. However, it is unclear whether increased abundance of antibiotic resistance genes in sewage and sewage-impacted environments is due to on-site selection pressure by residual antibiotics, or is simply a result of fecal contamination with resistant bacteria. Here we analyze relative resistance gene abundance and accompanying extent of fecal pollution in publicly available metagenomic data, using crAssphage sequences as a marker of human fecal contamination (crAssphage is a bacteriophage that is exceptionally abundant in, and specific to, human feces). We find that the presence of resistance genes can largely be explained by fecal pollution, with no clear signs of selection in the environment, with the exception of environments polluted by very high levels of antibiotics from manufacturing, where selection is evident. Our results demonstrate the necessity to take into account fecal pollution levels to avoid making erroneous assumptions regarding environmental selection of antibiotic resistance.

          Abstract

          Increased abundance of antibiotic resistance genes in the environment may be due to selection pressure by residual antibiotics, or to contamination with resistant bacteria from human faeces. Here, Karkman et al. analyze metagenomic data and find evidence supporting the second scenario in most cases.

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          Most cited references53

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          Tackling antibiotic resistance: the environmental framework.

          Antibiotic resistance is a threat to human and animal health worldwide, and key measures are required to reduce the risks posed by antibiotic resistance genes that occur in the environment. These measures include the identification of critical points of control, the development of reliable surveillance and risk assessment procedures, and the implementation of technological solutions that can prevent environmental contamination with antibiotic resistant bacteria and genes. In this Opinion article, we discuss the main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment.
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            Microbiological effects of sublethal levels of antibiotics.

            The widespread use of antibiotics results in the generation of antibiotic concentration gradients in humans, livestock and the environment. Thus, bacteria are frequently exposed to non-lethal (that is, subinhibitory) concentrations of drugs, and recent evidence suggests that this is likely to have an important role in the evolution of antibiotic resistance. In this Review, we discuss the ecology of antibiotics and the ability of subinhibitory concentrations to select for bacterial resistance. We also consider the effects of low-level drug exposure on bacterial physiology, including the generation of genetic and phenotypic variability, as well as the ability of antibiotics to function as signalling molecules. Together, these effects accelerate the emergence and spread of antibiotic-resistant bacteria among humans and animals.
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              Urban wastewater treatment plants as hotspots for antibiotic resistant bacteria and genes spread into the environment: a review.

              Urban wastewater treatment plants (UWTPs) are among the main sources of antibiotics' release into the environment. The occurrence of antibiotics may promote the selection of antibiotic resistance genes (ARGs) and antibiotic resistant bacteria (ARB), which shade health risks to humans and animals. In this paper the fate of ARB and ARGs in UWTPs, focusing on different processes/technologies (i.e., biological processes, advanced treatment technologies and disinfection), was critically reviewed. The mechanisms by which biological processes influence the development/selection of ARB and ARGs transfer are still poorly understood. Advanced treatment technologies and disinfection process are regarded as a major tool to control the spread of ARB into the environment. In spite of intense efforts made over the last years to bring solutions to control antibiotic resistance spread in the environment, there are still important gaps to fill in. In particular, it is important to: (i) improve risk assessment studies in order to allow accurate estimates about the maximal abundance of ARB in UWTPs effluents that would not pose risks for human and environmental health; (ii) understand the factors and mechanisms that drive antibiotic resistance maintenance and selection in wastewater habitats. The final objective is to implement wastewater treatment technologies capable of assuring the production of UWTPs effluents with an acceptable level of ARB. Copyright © 2013 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                antti.karkman@helsinki.fi
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                8 January 2019
                8 January 2019
                2019
                : 10
                : 80
                Affiliations
                [1 ]ISNI 0000 0000 9919 9582, GRID grid.8761.8, Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, , University of Gothenburg, ; Guldhedsgatan 10, SE-413 46 Gothenburg, Sweden
                [2 ]ISNI 0000 0000 9919 9582, GRID grid.8761.8, Center for Antibiotic Resistance research (CARe) at University of Gothenburg, ; P.O. Box 440, SE-40530 Gothenburg, Sweden
                [3 ]ISNI 0000 0004 0410 2071, GRID grid.7737.4, Faculty of Biological and Environmental Sciences, , University of Helsinki, ; Helsinki, 00014 Finland
                [4 ]ISNI 0000 0004 0410 2071, GRID grid.7737.4, Department of Microbiology, , University of Helsinki, ; Helsinki, 00014 Finland
                Author information
                http://orcid.org/0000-0003-0983-3319
                http://orcid.org/0000-0002-5496-0328
                Article
                7992
                10.1038/s41467-018-07992-3
                6325112
                30622259
                960ff713-5c48-4058-9186-ae6da2e9ab04
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 June 2018
                : 5 December 2018
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