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      The human microbiome as a reservoir of antimicrobial resistance

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          Abstract

          The gut microbiota is amongst the most densely populated microbial ecosystem on earth. While the microbiome exerts numerous health beneficial functions, the high density of micro-organisms within this ecosystem also facilitates horizontal transfer of antimicrobial resistance (AMR) genes to potential pathogenic bacteria. Over the past decades antibiotic susceptibility testing of specific indicator bacteria from the microbiome, such as Escherichia coli, has been the method of choice in most studies. These studies have greatly enlarged our understanding on the prevalence and distribution of AMR and associated risk factors. Recent studies using (functional) metagenomics, however, highlighted the unappreciated diversity of AMR genes in the human microbiome and identified genes that had not been described previously. Next to metagenomics, more targeted approaches such as polymerase chain reaction for detection and quantification of AMR genes within a population are promising, in particular for large-scale epidemiological screening. Here we present an overview of the indigenous microbiota as a reservoir of AMR genes, the current knowledge on this “resistome” and the recent and upcoming advances in the molecular diagnostic approaches to unravel this reservoir.

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          Most cited references48

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          Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.

          Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms. It is thought that an inflammatory response to commensal bacteria is avoided due to sequestration of microflora by surface epithelia. Here, we show that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis. Furthermore, we find that activation of TLRs by commensal microflora is critical for the protection against gut injury and associated mortality. These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions.
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            Resistance plasmid families in Enterobacteriaceae.

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              Comparative Analysis of Human Gut Microbiota by Barcoded Pyrosequencing

              Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.
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                Author and article information

                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                17 April 2013
                2013
                : 4
                : 87
                Affiliations
                Department of Medical Microbiology, Maastricht University Medical Centre+ Maastricht, Netherlands
                Author notes

                Edited by: Henk Aarts, National Institute for Public Health and the Environment, Netherlands

                Reviewed by: Henk Aarts, National Institute for Public Health and the Environment, Netherlands; Sabeel Padinhara Valappil, The University of Liverpool, UK

                *Correspondence: John Penders, Department of Medical Microbiology, Maastricht University Medical Centre+, P. O. Box 5800, 6202 AZ, Maastricht, Netherlands. e-mail: j.penders@ 123456maastrichtuniversity.nl

                This article was submitted to Frontiers in Antimicrobials, Resistance and Chemotherapy, a specialty of Frontiers in Microbiology.

                Article
                10.3389/fmicb.2013.00087
                3627978
                23616784
                197e001f-be50-4420-bf2d-ea519c1102f0
                Copyright © Penders, Stobberingh, Savelkoul and Wolffs.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 28 December 2012
                : 27 March 2013
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 71, Pages: 7, Words: 0
                Categories
                Microbiology
                Mini Review Article

                Microbiology & Virology
                gut microbiota,antimicrobial resistance,resistome,metagenomics,microbiome
                Microbiology & Virology
                gut microbiota, antimicrobial resistance, resistome, metagenomics, microbiome

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