Molecular characterization of blaNDM-harboring plasmids reveal its rapid adaptation and evolution in the Enterobacteriaceae.

Carbapenem is one of the few available drugs to treat multidrug-resistance Gram-negative bacteria infections. Recently, the plasmid-mediated spread of the carbapenem resistance gene bla_NDM poses a significant threat to public health, requiring global monitoring and surveillance. Here, we used both short-read (n = 2461) and long-read (n = 546) sequencing data to characterize the global distribution of bla_NDM. We analyzed the replicon type of bla_NDM-positive plasmids and found that the dominant plasmid type was different in diverse geographical locations. Although bla_NDM gene has been transferred across diverse countries, its genetic backgrounds are highly conserved, and the mobile genetic element ISAba125, IS5, and IS26 may play an important role in the mobilization of bla_NDM. A significant association was observed between host origin and gene presence/deletion variation on IncX3 plasmid, which may be a key factor in the bacterial adaption to diverse hosts. In this study, we analyzed the diversity, distribution and transmission of bla_NDM-positive plasmids from a global perspective, and emphasize the importance of plasmid analysis for understanding the evolution and adaptation of bla_NDM-positive plasmids and their co-evolution with bacterial genomes (resistome). [ABSTRACT FROM AUTHOR]