Occurrence of Carrying and in Southern China: New Insights in the Evolution of Megaplasmid IMP-26.

The spread of multidrug-resistant enterobacteria strains has posed a significant concern in public health, especially when the strain harbors metallo-beta-lactamase (MBL)-encoding and mobilized colistin resistance () genes as such genetic components potentially mediate multidrug resistance. Here we report an IncHI2/2A plasmid carrying and in multidrug-resistant human isolates YL4. Antimicrobial susceptibility testing was performed by the broth microdilution method. According to the results, YL4 was resistant to several antimicrobials, including β-lactams, fluorquinolones, sulfanilamide, glycylcycline, and aminoglycosides, except for amikacin. To investigate the plasmid further, we conducted whole-genome sequencing and sequence analysis. As shown, YL4 possessed a circular chromosome with 5,171,477 bp length and two plasmids, pYL4.1 (321,744 bp) and pYL4.2 (46,771 bp). Importantly, sharing high similarity with plasmids pZHZJ1 and pIMP-26, pYL4.1 has an IncHI2/2A backbone holding a variable region containing , , and two copies of . After comprehensively comparing relevant plasmids, we proposed an evolutionary pathway originating from ancestor pZHZJ1. Then, via an acquisition of the element and a few recombination events, this plasmid eventually evolved into pYL4.1 and pIMP-26 through two different pathways. In addition, the phage-like plasmid pYL4.2 also carried a gene. Remarkably, this study first identified a multidrug-resistant strain co-harboring and on a megaplasmid pYL4.1 and also included a proposed evolutionary pathway of epidemic megaplasmids carrying .