IS 26 Is Responsible for the Evolution and Transmission of bla NDM -Harboring Plasmids in Escherichia coli of Poultry Origin in China.

Carbapenem-resistant Enterobacteriaceae are some of the most important pathogens responsible for nosocomial infections, which can be challenging to treat. The bla _NDM carbapenemase genes, which are expressed by New Delhi metallo-β-lactamase (NDM)-producing Escherichia coli isolates, have been found in humans, environmental samples, and multiple other sources worldwide. Importantly, these genes have also been found in farm animals, which are considered an NDM reservoir and an important source of human infections. However, the dynamic evolution of bla _NDM genetic contexts and bla _NDM -harboring plasmids has not been directly observed, making it difficult to assess the extent of horizontal dissemination of the bla _NDM gene. In this study, we detected NDM-1 ( n = 1), NDM-5 ( n = 24), and NDM-9 ( n = 8) variants expressed by E. coli strains isolated from poultry in China from 2016 to 2017. By analyzing the immediate genetic environment of the bla _NDM genes, we found that IS 26 was associated with multiple types of bla _NDM multidrug resistance regions, and we identified various IS 26 -derived circular intermediates. Importantly, in E. coli strain GD33, we propose that IncHI2 and IncI1 plasmids can fuse when IS 26 is present. Our analysis of the IS 26 elements flanking bla _NDM allowed us to propose an important role for IS 26 elements in the evolution of multidrug-resistant regions (MRRs) and in the dissemination of bla _NDM . To the best of our knowledge, this is the first description of the dynamic evolution of bla _NDM genetic contexts and bla _NDM -harboring plasmids. These findings could help proactively limit the transmission of these NDM-producing isolates from food animals to humans. IMPORTANCE Carbapenem resistance in members of the order Enterobacterales is a growing public health problem that is associated with high mortality in developing and industrialized countries. Moreover, in the field of veterinary medicine, the occurrence of New Delhi metallo-β-lactamase-producing Escherichia coli isolates in animals, especially food-producing animals, has become a growing concern in recent years. The wide dissemination of bla _NDM is closely related to mobile genetic elements (MGEs) and plasmids. Although previous analyses have explored the association of many different MGEs with mobilization of bla _NDM , little is known about the evolution of various genetic contexts of bla _NDM in E. coli. Here, we report the important role of IS 26 in forming multiple types of bla _NDM multidrug resistance cassettes and the dynamic recombination of plasmids bearing bla _NDM . These results suggest that significant attention should be paid to monitoring the transmission and further evolution of bla _NDM -harboring plasmids among E. coli strains of food animal origin.