IS26 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 IS26 was associated with multiple types of bla(NDM) multidrug resistance regions, and we identified various IS26-derived circular intermediates. Importantly, in E. coli strain GD33, we propose that IncHI2 and IncI1 plasmids can fuse when IS26 is present. Our analysis of the IS26 elements flanking bla(NDM) allowed us to propose an important role for IS26 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 IS26 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.