机构:[1]Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China,[2]Department of Clinical Laboratory, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin, China,[3]Department of Clinical Laboratory, The Fifth People’s Hospital of Suzhou, Suzhou, China,[4]Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China,[5]Public Health Research Institute Tuberculosis Center, New Jersey Medical School, Rutgers University, Newark, NJ, United States,[6]Memorial Sloan Kettering Cancer Center, New York, NY, United States,[7]Department of Clinical Laboratory, The North District of Affiliated Suzhou Hospital, Nanjing Medical University, Suzhou, China
The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is increasing globally, with different molecular mechanisms described. Here we studied the molecular mechanisms of carbapenem resistance, including clonal and plasmid dissemination, of 67 CRE isolates collected between 2012 and 2016 from a tertiary hospital in Eastern China, an CRE endemic region. Species identification and susceptibility testing were performed using the BD Phoenix Automated Microbiology System. Isolates were characterized by PCR (for carbapenemases, ESBLs, AmpC and porin genes), multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and conjugation transfer experiments. Selected bla(KPC-2) -harboring plasmids were subjected to next-generation sequencing using the Illumina Miseq platform. Among the 67 CRE isolates, 42 Klebsiella pneumoniae, 10 Serratia marcescens, 6 Enterobacter cloacae, 2 Raoultella ornithinolytica, 2 K. oxytoca, 1 K. aerogenes, and 4 Escherichia coli isolates were identified. Six different carbapenemases were detected, including bla(KPC-2) (n = 45), bla(KPC-3) (n = 1), bla(NDM-1) (n = 6), bla(NDM-5) (n = 1), bla(IMP-4) = 2), and bla(VIM -1 )(n= 2); bla(OXA-48) -like genes were not detected. One E. cloacae strain possessed both bIa(NDM-1) and bla(KPC-3), while two E. cloacae isolates harbored bla(NDM-1) and bla(VIM-1). ESBLs (CTX-M, SHV, and TEM) and/or AmpC (CMY, DHA, and ACT/MIR) genes were also identified in 59 isolates, including 13 strains that lacked carbapenemases. Several insertions or stop codon mutations were found within porin genes of K. pneumoniae, E. coli and S. marcescens isolates, both with and without carbapenemases. The 42 K. pneumoniae isolates belonged to 12 different sequence types (ST), with ST11 being the most common, while the 6 E. cloacae isolates comprised 4 different STs. The 10 S. marcescens all shared the same PFGE pulsotype, suggestive of clonal spread. Complete plasmid sequencing and PCR screening revealed both intra-strain and inter-species spread of a common bla(KPC-2 )-harboring plasmid in our hospital. Taken together, our study revealed extensive genetic diversity among CRE isolates form a single Chinese hospital. CRE isolates circulating in the hospital differ significantly in their species, STs, porin genes, carbapenemase genes, and their plasmid content, highlighting the complex dissemination of CRE in this endemic region.
基金:
This study was supported by the National Natural Science
Foundation of China (81572032), Six Talent Peaks Project
in Jiangsu Province (2016-WSN-112), Key Research and
Development Project of Jiangsu Provincial Science and
Technology Department (BE2017654), Gusu Key Health
Talent of Suzhou, Jiangsu Youth Medical Talents Program
(QN-866, 867), and the Science and Technology Program of
Suzhou (SZS201715, SYS201619, and SYSD2018145). This
work was in part supported by the following grants from the
National Institutes of Health (R01AI090155, R21AI117338, and
P30CA008748).
第一作者机构:[1]Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China,[2]Department of Clinical Laboratory, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin, China,
共同第一作者:
通讯作者:
通讯机构:[1]Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China,[7]Department of Clinical Laboratory, The North District of Affiliated Suzhou Hospital, Nanjing Medical University, Suzhou, China
推荐引用方式(GB/T 7714):
Miao Minhui,Wen Huiyan,Xu Ping,et al.Genetic Diversity of Carbapenem-Resistant Enterobacteriaceae (CRE) Clinical Isolates From a Tertiary Hospital in Eastern China[J].FRONTIERS IN MICROBIOLOGY.2019,9(JAN):3341.doi:10.3389/fmicb.2018.03341.
APA:
Miao, Minhui,Wen, Huiyan,Xu, Ping,Niu, Siqiang,Lv, Jingnan...&Chen, Liang.(2019).Genetic Diversity of Carbapenem-Resistant Enterobacteriaceae (CRE) Clinical Isolates From a Tertiary Hospital in Eastern China.FRONTIERS IN MICROBIOLOGY,9,(JAN)
MLA:
Miao, Minhui,et al."Genetic Diversity of Carbapenem-Resistant Enterobacteriaceae (CRE) Clinical Isolates From a Tertiary Hospital in Eastern China".FRONTIERS IN MICROBIOLOGY 9..JAN(2019):3341