Reginal dissemination of transferable repB(1701) plasmid carrying blaNDM-4 in Asia: emergence of tandem repeats with blaNDM-4 mediated by IS26 in Klebsiella pneumoniae

Abstract The worldwide spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) has led to a major challenge to human health. The emergence and prevalence of transferable plasmid carrying carbapenemase encoding gene is undoubtedly a potential factor in increasing the burden of carbapenem resistance. In this study, we described the reginal dissemination of repB(1701) plasmid carrying blaNDM-4 in China, with the coexistence of blaNDM-4and blaOXA-9 in two independent K. pneumoniae isolates for the first time. Whole-genome sequencing and plasmid characterization of isolates L2388 and L3835 showed both blaNDM-4 and blaOXA-9 genes are situated on the transferable plasmid, designated as pL2388-NDM-OXA[120,100 bp, IncFII(K)-repB(R1701)] and pL3835-NDM-OXA [127,486 bp, repB(R1701)]. Notably, two copies of blaNDM-4 were identified in different orientations within pL3835-NDM-OXA. The blaNDM-4sequence is relatively conserved (blaNDM-₄-ble-trpF-dsbD-cutA-groES-groL), with various mobile genetic elements (MEGs) surrounding it, particularly IS26, which may play a pivotal role in gene-level dissemination. The previously unrecognized distribution of these plasmids across select regions of Southern China and Vietnam suggests a potentially wider epidemiological range than initially presumed in the context of microbiology and epidemiology. This is the first report of transferable IncFII(K)-repB(R1701)/repB(R1701) plasmids carrying the blaNDM-4 gene, relevant detection and investigation measures should be taken to control the prevalence.