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      The IncP-6 Plasmid p10265-KPC from Pseudomonas aeruginosa Carries a Novel ΔIS Ec33-Associated bla KPC-2 Gene Cluster

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          Abstract

          Pseudomonas aeruginosa strain 10265 was recovered from a patient with pneumonia in a Chinese public hospital, and it displays the carbapenem resistance phenotype due to the acquisition of a non-conjugative but mobilizable IncP-6-type plasmid p10265-KPC. p10265-KPC carries a Tn 5563-borne defective mer locus, and a novel ΔIS Ec33-associated bla KPC-2 gene cluster without paired inverted repeats and paired direct repeats at both ends. Mobilization of this ΔIS Ec33-associated element in p10265-KPC would be attributed to homologous recombination-based insertion of a foreign structure Tn 3-IS Apu1- orf7-IS Apu2- IS Kpn27-Δ bla TEM-1 -bla KPC-2 -ΔIS Kpn6- korC-orf6- klcA-Δ repB into a pre-existent intact IS Ec33, making IS Ec33 truncated at the 3′ end. The previously reported pCOL-1 represents the first sequenced KPC-producing IncP-6 plasmid, while p10265-KPC is the second one. These two plasmids carry two distinct bla KPC-2 gene clusters, which are inserted into the different sites of the IncP-6 backbone and have different evolutionary histories of assembly and mobilization. This is the first report of identification of the IncP-6-type resistance plasmid in China.

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          Most cited references26

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          Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding.

          Klebsiella pneumoniae carbapenemases (KPCs) were first identified in 1996 in the USA. Since then, regional outbreaks of KPC-producing K. pneumoniae (KPC-Kp) have occurred in the USA, and have spread internationally. Dissemination of blaKPC involves both horizontal transfer of blaKPC genes and plasmids, and clonal spread. Of epidemiological significance, the international spread of KPC-producing K. pneumoniae is primarily associated with a single multilocus sequence type (ST), ST258, and its related variants. However, the molecular factors contributing to the success of ST258 largely remain unclear. In this review, we discuss the recent progresses in understanding KPC-producing K. pneumoniae that are contributing to our knowledge of plasmid and genome composition and structure among the KPC epidemic clone, and we identify possible factors that influence its epidemiological success. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            A classification scheme for mobilization regions of bacterial plasmids.

            Transmissible plasmids can be classified according to their mobilization ability, as being conjugative (self-transmissible) or mobilizable (transmissible only in the presence of additional conjugative functions). Naturally occurring mobilizable plasmids carry the genetic information necessary for relaxosome formation and processing, but lack the functions required for mating pair formation. Mobilizable plasmids have a tremendous impact in horizontal gene transfer in nature, including the spread of antibiotic resistance. However, analysis of their promiscuity and diversity has attracted less attention than that of conjugative plasmids. This review will focus on the analysis of the diversity of mobilizable plasmids. For this purpose, we primarily compared the amino acid sequences of their relaxases and, when pertinent, we compared these enzymes with conjugative plasmid relaxases. In this way, we established phylogenetic relationships among the members of each superfamily. We conducted a database and literature analysis that led us to propose a classification system for small mobilizable plasmids in families and superfamilies according to their mobilization regions. This review outlines the genetic organization of each family of mobilization regions, as well as the most relevant properties and relationships among their constituent encoded proteins. In this respect, the present review constitutes a first approach to the characterization of the global gene pool of mobilization regions of small mobilizable plasmids.
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              First identification of Pseudomonas aeruginosa isolates producing a KPC-type carbapenem-hydrolyzing beta-lactamase.

              In Medellin, Colombia, three Pseudomonas aeruginosa isolates with high-level carbapenem resistance (MIC>or=256 microg/ml) and an isolate of Citrobacter freundii with reduced susceptibility to imipenem produced the plasmid-mediated class A carbapenemase KPC-2. This is the first report of a KPC-type beta-lactamase identified outside of the family Enterobacteriaceae.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                10 March 2016
                2016
                : 7
                : 310
                Affiliations
                [1] 1Department of Pulmonology, Southwest Hospital, Third Military Medical University Chongqing, China
                [2] 2State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China
                [3] 3Department of Pharmacy, Southwest Hospital, Third Military Medical University Chongqing, China
                Author notes

                Edited by: Gilberto Igrejas, University of Trás-os-Montes and Alto Douro, Portugal

                Reviewed by: Christopher Morton Thomas, University of Birmingham, UK; Alain Hartmann, Institut National de la Recherche Agronomique, France; Xian-Zhi Li, Health Canada, Canada

                *Correspondence: Xiangdong Zhou, xiangdongzhou@ 123456126.com ; Fengjun Sun, fengj_sun@ 123456163.com

                This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2016.00310
                4785139
                27014233
                da7e62c1-030c-4e53-97b3-061321d5ecdb
                Copyright © 2016 Dai, Zhou, Xiong, Feng, Luo, Luo, Wang, Sun and Zhou.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 November 2015
                : 25 February 2016
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 29, Pages: 9, Words: 0
                Categories
                Microbiology
                Original Research

                Microbiology & Virology
                pseudomonas aeruginosa,kpc-2,p10265-kpc,incp-6
                Microbiology & Virology
                pseudomonas aeruginosa, kpc-2, p10265-kpc, incp-6

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