國家衛生研究院 NHRI:Item 3990099045/7176
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/7176


    Title: Copy number change of the NDM-1 sequence in a multidrug-resistant Klebsiella pneumoniae clinical isolate
    Authors: Huang, TW;Chen, TL;Chen, YT;Lauderdale, TL;Liao, TL;Lee, YT;Chen, CP;Liu, YM;Lin, AC;Chang, YH;Wu, KM;Kirby, R;Lai, JF;Tan, MC;Siu, LK;Chang, CM;Fung, CP;Tsai, SF
    Contributors: Institute of Molecular and Genomic Medicine;Division of Infectious Diseases
    Abstract: The genetic features of the antimicrobial resistance of a multidrug resistant Klebsiella pneumoniae strain harboring blaNDM-1 were investigated to increase our understanding of the evolution of NDM-1. The strain, KPX, came from a Taiwanese patient with a hospitalization history in New Delhi. Complete DNA sequencing was performed; and the genes responsible for antimicrobial resistance were systematically examined and isolated by library screening. KPX harbored two resistance plasmids, pKPX-1 and pKPX-2, which are 250-kb and 141-kb in size, respectively, with blaNDM-1 present on pKPX-1. The plasmid pKPX-1 contained genes associated with the IncR and IncF groups, while pKPX-2 belonged to the IncF family. Each plasmid carried multiple antimicrobial resistance genetic determinants. The gene responsible for resistance to carbapenems was found on pKPX-1 and that for resistance to aztreonam was found on pKPX-2. To our surprise, we discovered that blaNDM-1 exists on pKPX-1 as multiple copies in the form of tandem repeats. Amplification of blaNDM-1 was found to occur by duplication of an 8.6-kb unit, with the copy number of the repeat varying from colony to colony. This repeat sequence is identical to that of the pNDM-MAR except for two base substitutions. The copy number of blaNDM-1 of colonies under different conditions was assessed by Southern blotting and quantitative PCR. The blaNDM-1 sequence was maintained in the presence of the antimicrobial selection; however, removal of antimicrobial selection led to the emergence of susceptible bacterial populations with a reduced copy number or even the complete loss of the blaNDM-1 sequence. The dynamic nature of the NDM-1 sequence provides a strong argument for judicious use of the broad-spectrum antimicrobials in order to reduce the development and spread of antimicrobial resistance among pathogens.
    Date: 2013-04-29
    Relation: PLoS ONE. 2013 Apr 29;8(4):Article number e62774.
    Link to: http://dx.doi.org/10.1371/journal.pone.0062774
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1932-6203&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000321662800061
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84876929646
    Appears in Collections:[Shih-Feng Tsai] Periodical Articles
    [Chung-Ming Chang] Periodical Articles
    [Tsai-Ling Yang Lauderdale] Periodical Articles
    [Leung-Kei Siu] Periodical Articles

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