{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:44:25Z","timestamp":1788241465303,"version":"build-2803163510"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T00:00:00Z","timestamp":1580428800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T00:00:00Z","timestamp":1580428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Excellent Team of Young Teachers Foundation of Heilongjiang Province","award":["2018-KYYWF-0916"],"award-info":[{"award-number":["2018-KYYWF-0916"]}]},{"name":"Heilongjiang Provincial Health and Family Planning Commission on Scientific Research Project","award":["2018-290"],"award-info":[{"award-number":["2018-290"]}]},{"name":"Heilongjiang Provincial Health and Family Planning Commission on Scientific Research Project","award":["2018-291"],"award-info":[{"award-number":["2018-291"]}]},{"name":"Jiamusi University President Innovation and Entrepreneurship Fund Project","award":["XZYF2018-43"],"award-info":[{"award-number":["XZYF2018-43"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p><jats:italic>Enterobacter cloacae<\/jats:italic> complex (ECC) is one of the most common extended-spectrum \u03b2-lactamase and carbapenemase-producing pathogen that threatens millions of the elderly and vulnerable sick persons. The objective of this study was to perform the molecular characteristics of the carbapenem-resistant <jats:italic>E. cloacae<\/jats:italic> complex (CREC) emerged in Heilongjiang Province of China.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Six CREC strains were isolated from the patients with infectious diseases. The identities of ECC isolates were confirmed by sequencing the polymerase chain reaction (PCR) products of <jats:italic>16S rRNA<\/jats:italic> gene. The characterization of the CREC isolates were analyzed by sequencing PCR products of the <jats:italic>carbapenemase<\/jats:italic>, <jats:italic>ampC<\/jats:italic> and <jats:italic>fluoroquinolone<\/jats:italic> resistance genes and performing multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and whole genome sequencing.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>All 6 isolates harbored multiple resistance genes. Of them, 5 carried <jats:italic>metallo-\u03b2-lactamases<\/jats:italic> and one was <jats:italic>bla<\/jats:italic><jats:sub>KPC-2<\/jats:sub>-positive. The levofloxacin and ciprofloxacin-resistant strains had substitutions of <jats:italic>gyrA<\/jats:italic>83, <jats:italic>gyrA<\/jats:italic>87, and <jats:italic>parC<\/jats:italic>80 in the quinolone-resistance determining regions. The MLST analyses revealed that 6 isolates belonged to five sequence types (ST520, ST528, ST1119, ST1120, and ST93) while the PFGE patterns of the isolates fallen into four clusters. The strain ST1120 was found to carry two separated plasmids that encode <jats:italic>bla<\/jats:italic><jats:sub>NDM-1<\/jats:sub> and <jats:italic>bla<\/jats:italic><jats:sub>IMP-4<\/jats:sub>.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our study, for the first time, identified a CREC strain that co-produces <jats:italic>bla<\/jats:italic><jats:sub>NDM-1<\/jats:sub> and <jats:italic>bla<\/jats:italic><jats:sub>IMP-4<\/jats:sub> in the Northeast China. Our finding emphasizes an urgent need for more intensive surveillance and precaution measures to prevent the CERC spread.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12879-020-4768-7","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T16:03:51Z","timestamp":1580486631000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Molecular characterization of metallo-\u03b2-lactamase- producing carbapenem-resistant Enterobacter cloacae complex isolated in Heilongjiang Province of China"],"prefix":"10.1186","volume":"20","author":[{"given":"Yongxin","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,31]]},"reference":[{"key":"4768_CR1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/nyas.12537","volume":"1323","author":"E Temkin","year":"2014","unstructured":"Temkin E, Adler A, Lerner A, Carmeli Y. Carbapenem-resistant Enterobacteriaceae: biology, epidemiology, and management. Ann N Y Acad Sci. 2014;1323:22\u201342.","journal-title":"Ann N Y Acad Sci"},{"issue":"1","key":"4768_CR2","first-page":"15","volume":"3","author":"G Meletis","year":"2016","unstructured":"Meletis G. Carbapenem resistance: overview of the problem and future perspectives. Ther Adv Infect Dis. 2016;3(1):15\u201321.","journal-title":"Ther Adv Infect Dis"},{"issue":"6","key":"4768_CR3","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1097\/QCO.0000000000000608","volume":"32","author":"Adrian J. Brink","year":"2019","unstructured":"Brink AJ. Epidemiology of carbapenem-resistant gram-negative infections globally. Curr Opin Infect Dis. 2019;32(6):609-616. https:\/\/doi.org\/10.1097\/QCO.0000000000000608.","journal-title":"Current Opinion in Infectious Diseases"},{"issue":"10","key":"4768_CR4","doi-asserted-by":"publisher","first-page":"ofy241","DOI":"10.1093\/ofid\/ofy241","volume":"5","author":"E McCann","year":"2018","unstructured":"McCann E, Srinivasan A, DeRyke CA, Ye G, DePestel DD, Murray J, Gupta V, et al. Open Forum Infect Dis. 2018;5(10):ofy241.","journal-title":"Open Forum Infect Dis"},{"issue":"1","key":"4768_CR5","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/2047-2994-3-32","volume":"3","author":"D Nathwani","year":"2014","unstructured":"Nathwani D, Raman G, Sulham K, Gavaghan M, Menon V. Clinical and economic consequences of hospital-acquired resistant and multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis. Antimicrob Resist Infect Control. 2014;3(1):32.","journal-title":"Antimicrob Resist Infect Control"},{"issue":"7","key":"4768_CR6","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.3201\/eid2007.121004","volume":"20","author":"ME Falagas","year":"2014","unstructured":"Falagas ME, Tansarli GS, Karageorgopoulos DE, Vardakas KZ. Deaths attributable to carbapenem-resistant Enterobacteriaceae infections. Emerg Infect Dis. 2014;20(7):1170\u20135.","journal-title":"Emerg Infect Dis"},{"key":"4768_CR7","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.plasmid.2018.09.010","volume":"99","author":"M Dolejska","year":"2018","unstructured":"Dolejska M, Papagiannitsis CC. Plasmid-mediated resistance is going wild. Plasmid. 2018;99:99\u2013111.","journal-title":"Plasmid"},{"key":"4768_CR8","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3389\/fmicb.2019.00044","volume":"10","author":"MK Annavajhala","year":"2019","unstructured":"Annavajhala MK, Gomez-Simmonds A, Uhlemann AC. Multidrug-resistant Enterobacter cloacae Complex emerging as a global. Diversifying Threat Front Microbiol. 2019;10:44.","journal-title":"Diversifying Threat Front Microbiol"},{"issue":"6","key":"4768_CR9","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.3201\/eid2406.171648","volume":"24","author":"G Peirano","year":"2018","unstructured":"Peirano G, Matsumura Y, Adams MD, Bradford P, Motyl M, Chen L, Kreiswirth BN, Pitout JDD. Genomic epidemiology of global Carbapenemase-producing Enterobacter spp., 2008-2014. Emerg Infect Dis. 2018;24(6):1010\u20139.","journal-title":"Emerg Infect Dis"},{"key":"4768_CR10","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.3389\/fmicb.2018.01549","volume":"9","author":"V Paskova","year":"2018","unstructured":"Paskova V, Medvecky M, Skalova A, Chudejova K, Bitar I, Jakubu V, Bergerova T, Zemlickova H, Papagiannitsis CC, Hrabak J. Characterization of NDM-encoding plasmids from Enterobacteriaceae recovered from Czech hospitals. Front Microbiol. 2018;9:1549.","journal-title":"Front Microbiol"},{"issue":"2","key":"4768_CR11","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1128\/AEM.62.2.625-630.1996","volume":"62","author":"MT Suzuki","year":"1996","unstructured":"Suzuki MT, Giovannoni SJ. Bias caused by template annealing in the amplification of mixtures of 16S rRNA genes by PCR. Appl Environ Microbiol. 1996;62(2):625\u201330.","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"4768_CR12","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1186\/s12879-018-3294-3","volume":"18","author":"X Gong","year":"2018","unstructured":"Gong X, Zhang J, Su S, Fu Y, Bao M, Wang Y, Zhang X. Molecular characterization and epidemiology of carbapenem non-susceptible Enterobacteriaceae isolated from the eastern region of Heilongjiang Province. China BMC Infect Dis. 2018;18(1):417.","journal-title":"China BMC Infect Dis"},{"issue":"5","key":"4768_CR13","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1111\/j.1469-0691.2006.01389.x","volume":"12","author":"JM Rodriguez-Martinez","year":"2006","unstructured":"Rodriguez-Martinez JM, Velasco C, Pascual A, Garcia I, Martinez-Martinez L. Correlation of quinolone resistance levels and differences in basal and quinolone-induced expression from three qnrA-containing plasmids. Clin Microbiol Infect. 2006;12(5):440\u20135.","journal-title":"Clin Microbiol Infect"},{"issue":"10","key":"4768_CR14","first-page":"2052","volume":"45","author":"N Zhuang","year":"2012","unstructured":"Zhuang N, Chen X, Yue L, Liao X, Liu Y. Detection of PMQR gene in Escherichia coli isolated from animals. Sci Agric Sin. 2012;45(10):2052\u20137.","journal-title":"Sci Agric Sin"},{"issue":"9","key":"4768_CR15","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1128\/JCM.33.9.2233-2239.1995","volume":"33","author":"FC Tenover","year":"1995","unstructured":"Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, Swaminathan B. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995;33(9):2233\u20139.","journal-title":"J Clin Microbiol"},{"issue":"2","key":"4768_CR16","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S1473-3099(15)00424-7","volume":"16","author":"YY Liu","year":"2016","unstructured":"Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16(2):161\u20138.","journal-title":"Lancet Infect Dis"},{"issue":"3","key":"4768_CR17","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.diagmicrobio.2009.10.003","volume":"66","author":"Q Wu","year":"2010","unstructured":"Wu Q, Liu Q, Han L, Sun J, Ni Y. Plasmid-mediated carbapenem-hydrolyzing enzyme KPC-2 and ArmA 16S rRNA methylase conferring high-level aminoglycoside resistance in carbapenem-resistant Enterobacter cloacae in China. Diagn Microbiol Infect Dis. 2010;66(3):326\u20138.","journal-title":"Diagn Microbiol Infect Dis"},{"key":"4768_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.meegid.2012.10.010","volume":"14","author":"W Dai","year":"2013","unstructured":"Dai W, Sun S, Yang P, Huang S, Zhang X, Zhang L. Characterization of carbapenemases, extended spectrum beta-lactamases and molecular epidemiology of carbapenem-non-susceptible Enterobacter cloacae in a Chinese hospital in Chongqing. Infect Genet Evol. 2013;14:1\u20137.","journal-title":"Infect Genet Evol"},{"key":"4768_CR19","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.3389\/fmicb.2018.01597","volume":"9","author":"C Jin","year":"2018","unstructured":"Jin C, Zhang J, Wang Q, Chen H, Wang X, Zhang Y, Wang H. Molecular characterization of Carbapenem-resistant Enterobacter cloacae in 11 Chinese cities. Front Microbiol. 2018;9:1597.","journal-title":"Front Microbiol"},{"key":"4768_CR20","doi-asserted-by":"publisher","first-page":"16260","DOI":"10.1038\/nmicrobiol.2016.260","volume":"2","author":"Y Wang","year":"2017","unstructured":"Wang Y, Zhang R, Li J, Wu Z, Yin W, Schwarz S, Tyrrell JM, Zheng Y, Wang S, Shen Z, et al. Comprehensive resistome analysis reveals the prevalence of NDM and MCR-1 in Chinese poultry production. Nat Microbiol. 2017;2:16260.","journal-title":"Nat Microbiol"},{"key":"4768_CR21","first-page":"94","volume":"8","author":"Z Shi","year":"2017","unstructured":"Shi Z, Zhao H, Li G, Jia W. Molecular characteristics of Carbapenem-resistant Enterobacter cloacae in Ningxia Province. China Front Microbiol. 2017;8:94.","journal-title":"China Front Microbiol"},{"issue":"3","key":"4768_CR22","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.ijantimicag.2010.05.004","volume":"36","author":"I Galani","year":"2010","unstructured":"Galani I, Souli M, Mitchell N, Chryssouli Z, Giamarellou H. Presence of plasmid-mediated quinolone resistance in Klebsiella pneumoniae and Escherichia coli isolates possessing blaVIM-1 in Greece. Int J Antimicrob Agents. 2010;36(3):252\u20134.","journal-title":"Int J Antimicrob Agents"},{"issue":"1","key":"4768_CR23","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1054\/drup.1998.0068","volume":"2","author":"DC Hooper","year":"1999","unstructured":"Hooper DC. Mechanisms of fluoroquinolone resistance. Drug Resist Updat. 1999;2(1):38\u201355.","journal-title":"Drug Resist Updat"},{"issue":"Suppl 1","key":"4768_CR24","doi-asserted-by":"publisher","first-page":"S9","DOI":"10.1086\/319370","volume":"32","author":"DC Hooper","year":"2001","unstructured":"Hooper DC. Mechanisms of action of antimicrobials: focus on fluoroquinolones. Clin Infect Dis. 2001;32(Suppl 1):S9\u2013s15.","journal-title":"Clin Infect Dis"},{"issue":"10","key":"4768_CR25","volume":"3","author":"S Arredondo-Alonso","year":"2017","unstructured":"Arredondo-Alonso S, Willems RJ, van Schaik W, Schurch AC. On the (im) possibility of reconstructing plasmids from whole-genome short-read sequencing data. Microb Genom. 2017;3(10):e000128.","journal-title":"Microb Genom"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-020-4768-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12879-020-4768-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-020-4768-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T00:11:02Z","timestamp":1611965462000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-020-4768-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,31]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["4768"],"URL":"https:\/\/doi.org\/10.1186\/s12879-020-4768-7","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,31]]},"assertion":[{"value":"12 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the Ethics Committee of Jiamusi University Clinical Medical College for research. The committee\u2019s reference number is 20180326. Individual informed consent was waived by the ethics committee listed above because this study used currently existing sample collected during the course of routine medical care and did not cause any additional risks to the patients.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"94"}}