| TheemergenceofNewDelhimetallo-?-lactamase?NDM?in Enterobacteriaceae poses a serious threat to public health,and is widely disseminated in China.Our previous study of the carbapenem-resistant Enterobacteriaceae?CRE?bacteria isolated from Henan Province in 2011-2012,revealed that the high-risk epidemic and active transmission of NDM-producing Enterobacteriaceae strains.Here,we studied the molecular epidemiology and resistance mechanism of NDM-producing Enterobacteriaceae in Henan province,from 2013 to 2016,to explore the epidemic regularity of the NDM-producing Enterobacteriaceae bacteria and reveal the molecular mechanism of its dissemination.A total of 393 CRE strains were collected from a teaching hospital of Zhengzhou University from 2013 to 2016,of which 291?74%?produced KPC,87?22%?produced NDM,14?4%?produced IMP and only one produced OXA-48-like.KPC was predominant in Klebsiella pneumoniae?n=256,91.1%?,whereas NDM was predominant in Escherichia coli?n=43,49.2%?and the ST167 E.coli?n=18,41.9%?are the major epidemic clones.A total of five NDM subtypes including NDM-1,-4,-5,-7 and-9 were detected,of which the predominant subtypes were NDM-1?49.4%?and NDM-5?46.0%?.The minimal inhibitory concentration results showed that the NDM-producing CRE strains were multi-drug resistant and even extensively drug resistant bacteria,and carried a variety of drug resistance genes.The patients of middle-aged and infants were mainly infected population with blaNDMDM isolates and61%patients were male.Urine,sputum and blood were the main source of blaNDMDM strains.Lower respiratory tract infections were the most common disease.These strains were the most frequently detected in intensive care units?ICU?.The mortality rate of blaNDM-positive CRE isolates was 19.54%.S1-PFGE and Southern hybridization revealed that the most of the blaNDMDM gene were located on plasmids.In this study,the blaNDM-harboring plasmids belong to 5replicon types.IncX3?n=70?was the predominate type,followed by IncFII?n=7?and IncA/C?n=5?.Meanwhile,this is the first report of IncQ1 and IncI1 plasmids carrying blaNDMDM gene.Complete sequencing of plasmids indicated that the IncX3plasmids carrying blaNDMDM were high conserved in the backbone regions compare with a previously reported plasmid,pNDM-HN380?GeneBank number:JX104760?.Conjugation assays showed that the IncX3 plasmids were readily transferred to the recipient cells at higher frequencies the IncFII or IncA/C plasmids.A novel blaNDM-5harboring F2:A-:B-plasmid,pNDM-EC16-50,which might have evolved from a recombination of the well reported pMC-NDM-like plasmid and locally emerged pSJ49 plasmid.The backbone region of IncA/C type plasmids have higher homology with that of the blaNDM-bearing IncA/C type plasmids reported previously,but the mosaic regions carrying resistance genes were varied.In addition,our study reported two novel blaNDM-carrying plasmids,which belonged to IncQ1 and IncI1types,indicating the further spread of blaNDMDM gene.The blaNDMDM gene was not only present on the plasmid but also detected on the chromosome.The Providencia rettgeri strain Pr-15-2-50 was found carried two tandem copies of bla NDM-1DM-1 on the chromosome and the blaNDM-1DM-1 gene in Proteus mirabilis PM-13-58 were present on both plasmids and chromosomes,and the same genetic backgrounds of blaNDM-1DM-1 gene,indicating that ISCR1 element plays an important role in dissemination of bla NDMDM genes.In summary,this study demonstrated that the blaNDMDM gene can be captured by a variety of plasmids belonged to different Inc types.Among which,the IncX3 plasmid played an vital role in the dissemination of blaNDMDM gene and the ISCR1 element was responsible for the transmission of blaNDMDM gene between plasmids and chromosomes. |
PDF Full Text Request