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      Rarity of mcr-1-positive Bacteria in Patients with Blood Infection is not a Reason to Ignore its Significance in Clinical Practice

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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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            Prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae recovered from bloodstream infections in China: a multicentre longitudinal study.

            Polymyxin antibiotics are used as last-resort therapies to treat infections caused by multidrug-resistant Gram-negative bacteria. The plasmid-mediated colistin resistance determinant MCR-1 has been identified in Enterobacteriaceae in China. We did this study to investigate the prevalence of the mcr-1 gene in clinical isolates from patients with bloodstream infections in China.
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              Dissemination and Mechanism for the MCR-1 Colistin Resistance

              Polymyxins are the last line of defense against lethal infections caused by multidrug resistant Gram-negative pathogens. Very recently, the use of polymyxins has been greatly challenged by the emergence of the plasmid-borne mobile colistin resistance gene (mcr-1). However, the mechanistic aspects of the MCR-1 colistin resistance are still poorly understood. Here we report the comparative genomics of two new mcr-1-harbouring plasmids isolated from the human gut microbiota, highlighting the diversity in plasmid transfer of the mcr-1 gene. Further genetic dissection delineated that both the trans-membrane region and a substrate-binding motif are required for the MCR-1-mediated colistin resistance. The soluble form of the membrane protein MCR-1 was successfully prepared and verified. Phylogenetic analyses revealed that MCR-1 is highly homologous to its counterpart PEA lipid A transferase in Paenibacili, a known producer of polymyxins. The fact that the plasmid-borne MCR-1 is placed in a subclade neighboring the chromosome-encoded colistin-resistant Neisseria LptA (EptA) potentially implies parallel evolutionary paths for the two genes. In conclusion, our finding provids a first glimpse of mechanism for the MCR-1-mediated colistin resistance.
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                Author and article information

                Contributors
                Journal
                Infectious Diseases and Translational Medicine
                Infect. Dis. Transl. Med.
                Infect. Dis. Transl. Med.
                International Biological and Medical Journals Publishing House Co., Limited (Room E16, 3/f, Yongda Commercial Building, No.97, Bonham Stand (Sheung Wan), HongKong )
                2411-2917
                14 March 2017
                14 March 2017
                : 3
                : 1
                : 3-4
                Affiliations
                From Beijing Hospital of Traditional Chinese Medicine, No. 23, MeishuguanhouStreet, Beijing 100010, China
                Author notes
                Correspondence to: Chao Yang, Email: wishyc5@ 123456163.com .
                Article
                10.11979/idtm.201701002
                c9d7c445-031b-4c41-8354-86348446ca9b

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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                Figures: 0, Tables: 0, References: 9, Pages: 2
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                Medicine,Infectious disease & Microbiology
                Medicine, Infectious disease & Microbiology

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