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

Xiaofeng Hu¹Boqian Wang²Mingliang Chen³Kexin Li¹Zhixi Peng¹Lianqun Jin¹Junjie Yue²Hui Chen¹Ling Zhang¹Shaofu Qiu¹Hongguang Ren^2*Hongbin Song¹

• ¹Chinese PLA Center for Disease Control and Prevention, Beijing, China
• ²Beijing Institute of Biotechnology, Fengtai, Beijing, China
• ³Army Medical University, Chongqing, China

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 .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 livestockenvironment-human transmission cycle, while the phylogenetic diversity of bla NDM and tet(X)-cocarrying 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.