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      Mobile resistome of human gut and pathogen drives anthropogenic bloom of antibiotic resistance

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          Abstract

          Background

          The impact of human activities on the environmental resistome has been documented in many studies, but there remains the controversial question of whether the increased antibiotic resistance observed in anthropogenically impacted environments is just a result of contamination by resistant fecal microbes or is mediated by indigenous environmental organisms. Here, to determine exactly how anthropogenic influences shape the environmental resistome, we resolved the microbiome, resistome, and mobilome of the planktonic microbial communities along a single river, the Han, which spans a gradient of human activities.

          Results

          The bloom of antibiotic resistance genes (ARGs) was evident in the downstream regions and distinct successional dynamics of the river resistome occurred across the spatial continuum. We identified a number of widespread ARG sequences shared between the river, human gut, and pathogenic bacteria. These human-related ARGs were largely associated with mobile genetic elements rather than particular gut taxa and mainly responsible for anthropogenically driven bloom of the downstream river resistome. Furthermore, both sequence- and phenotype-based analyses revealed environmental relatives of clinically important proteobacteria as major carriers of these ARGs.

          Conclusions

          Our results demonstrate a more nuanced view of the impact of anthropogenic activities on the river resistome: fecal contamination is present and allows the transmission of ARGs to the environmental resistome, but these mobile genes rather than resistant fecal bacteria proliferate in environmental relatives of their original hosts.

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          Most cited references22

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          Sampling the antibiotic resistome.

          Microbial resistance to antibiotics currently spans all known classes of natural and synthetic compounds. It has not only hindered our treatment of infections but also dramatically reshaped drug discovery, yet its origins have not been systematically studied. Soil-dwelling bacteria produce and encounter a myriad of antibiotics, evolving corresponding sensing and evading strategies. They are a reservoir of resistance determinants that can be mobilized into the microbial community. Study of this reservoir could provide an early warning system for future clinically relevant antibiotic resistance mechanisms.
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            Bacterial phylogeny structures soil resistomes across habitats

            Summary Ancient and diverse antibiotic resistance genes (ARGs) have previously been identified from soil 1–3 , including genes identical to those in human pathogens 4 . Despite the apparent overlap between soil and clinical resistomes 4–6 , factors influencing ARG composition in soil and their movement between genomes and habitats remain largely unknown 3 . General metagenome functions often correlate with the underlying structure of bacterial communities 7–12 . However, ARGs are hypothesized to be highly mobile 4,5,13 , prompting speculation that resistomes may not correlate with phylogenetic signatures or ecological divisions 13,14 . To investigate these relationships, we performed functional metagenomic selections for resistance to 18 antibiotics from 18 agricultural and grassland soils. The 2895 ARGs we discovered were predominantly novel, and represent all major resistance mechanisms 15 . We demonstrate that distinct soil types harbor distinct resistomes, and that nitrogen fertilizer amendments strongly influenced soil ARG content. Resistome composition also correlated with microbial phylogenetic and taxonomic structure, both across and within soil types. Consistent with this strong correlation, mobility elements syntenic with ARGs were rare in soil compared to sequenced pathogens, suggesting that ARGs in the soil may not transfer between bacteria as readily as is observed in the clinic. Together, our results indicate that bacterial community composition is the primary determinant of soil ARG content, challenging previous hypotheses that horizontal gene transfer effectively decouples resistomes from phylogeny 13,14 .
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              Using the class 1 integron-integrase gene as a proxy for anthropogenic pollution

              Around all human activity, there are zones of pollution with pesticides, heavy metals, pharmaceuticals, personal care products and the microorganisms associated with human waste streams and agriculture. This diversity of pollutants, whose concentration varies spatially and temporally, is a major challenge for monitoring. Here, we suggest that the relative abundance of the clinical class 1 integron-integrase gene, intI1, is a good proxy for pollution because: (1) intI1 is linked to genes conferring resistance to antibiotics, disinfectants and heavy metals; (2) it is found in a wide variety of pathogenic and nonpathogenic bacteria; (3) its abundance can change rapidly because its host cells can have rapid generation times and it can move between bacteria by horizontal gene transfer; and (4) a single DNA sequence variant of intI1 is now found on a wide diversity of xenogenetic elements, these being complex mosaic DNA elements fixed through the agency of human selection. Here we review the literature examining the relationship between anthropogenic impacts and the abundance of intI1, and outline an approach by which intI1 could serve as a proxy for anthropogenic pollution.
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                Author and article information

                Contributors
                cjcha@cau.ac.kr
                Journal
                Microbiome
                Microbiome
                Microbiome
                BioMed Central (London )
                2049-2618
                7 January 2020
                7 January 2020
                2020
                : 8
                : 2
                Affiliations
                [1 ]ISNI 0000 0001 0789 9563, GRID grid.254224.7, Department of Systems Biotechnology and Center for Antibiotic Resistome, , Chung-Ang University, ; Anseong, 17546 Republic of Korea
                [2 ]ISNI 0000 0000 8809 1613, GRID grid.7372.1, School of Life Sciences, , University of Warwick, ; Coventry, CV4 7AL UK
                [3 ]ISNI 0000 0000 8809 1613, GRID grid.7372.1, Warwick Medical School, , University of Warwick, ; Coventry, CV4 7AL UK
                Author information
                http://orcid.org/0000-0002-2210-2898
                Article
                774
                10.1186/s40168-019-0774-7
                6947943
                31910889
                d42679e2-d35b-4eb3-964c-a65292f79b5e
                © The Author(s). 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 September 2019
                : 9 December 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003562, Ministry of Environment;
                Award ID: 2016001350004
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                antibiotic resistance,antibiotic resistance gene,resistome,mobile genetic element,horizontal gene transfer,human gut microbiome,pathogen,transmission,metagenome,bacterial genome

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