Evolution, dissemination, and genetic dynamics of the carbapenem resistance gene bla _NDM in China

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.

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.

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.

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.