Abstract
BACKGROUND: Bla (NDM), which encodes a metallo-β-lactamase that can hydrolyze most β-lactam antibiotics, has become a serious public health concern in China. It is crucial to investigate the evolution, dissemination, and genetic dynamics of bla (NDM) to develop potential strategies to control the proliferation of bla (NDM). METHODS: In this study, we collected 1021 bla (NDM)-positive isolates, which features 67 new genomes from our laboratory and 954 genomes from NCBI. Through epidemiological big data analysis, phylogenetic tree-based geographic transmission analysis, and upstream-downstream genetic clustering evolution analysis, we systematically analyzed the evolution, dissemination, and genetic dynamics of bla (NDM)-positive bacteria. RESULTS: Analysis results indicate that bla(NDM-5) is gradually supplanting bla (NDM-1) in China and Acinetobacter has been replaced as the primary bla (NDM)-harboring genus by the Enterobacter, Escherichia, and Klebsiella, which are both within the Enterobacteriaceae family and more easily transmitted among humans. Furthermore, bla (NDM)-positive bacteria exhibit a distinct livestock-environment-human transmission cycle, while the phylogenetic diversity of bla (NDM) and tet(X)-co-carrying genera is progressively expanding with concomitantly enhanced resistance phenotypes. Currently, the predominant bla (NDM)-positive bacterial strains have likely disseminated from southwest China to coastal regions. We further identified multiple transposon structures beyond Tn125 that may facilitate bla (NDM) transfer. CONCLUSIONS: The diversity of the bla (NDM) and its carrier bacterial strains is continuously increasing, and its transmission range is also expanding. Of greater concern, super-resistant strains co-harboring bla (NDM) and tet(X) genes exhibit high potential for imminent emergence in human populations. Considering that the bla (NDM)-carrier bacteria are increasingly adapted to inter-human spread, the analysis results above can provide methodological and data support for epidemiological surveillance, tracing, and early warning alerts.