Dynamic evolution and transmission of a blaNDM-1-bearing fusion plasmid in a clinical Escherichia coli.

Plasmids are the main driving forces for the rapid dissemination of blaNDM-1. In recent years, blaNDM-1-carrying fusion plasmids have been frequently reported. However, the evolutionary patterns of blaNDM-1-carrying fusion plasmids remain largely unknown. Herein, we reported a blaNDM-1-bearing fusion plasmid pZX35-269k possessing IncFII and IncA/C2 replicons from clinical ST349 E. coli 13ZX35. The backbone of pZX35-269k was structurally unstable, which was manifested in different types of structural dissociation during conjugation and passage, thereby forming various daughter plasmids. Moreover, the same events were observed in the clinical setting as well. We found that pZX35-269k exhibited highly identical to two plasmids (pZX30-70k and pZX30-192k) in 13ZX30, both of which were isolated from the same hospital. Sequence analysis highlighted that two plasmids in 13ZX30 evolved from pZX35-269k through homologous recombination of a 4856-bp fragment. Collectively, this study confirmed the transmission and structural evolution of a blaNDM-1-bearing fusion plasmid in both laboratory and clinical settings, and provided clear evidence of plasmid spread and evolution in clinical settings. Such versatile plasmids may represent a potential risk for the public health.