Transmission and stable inheritance of carbapenemase gene (bla_KPC-2 or bla_NDM-1)-encoding and mcr-1-encoding plasmids in clinical Enterobacteriaceae strains

Objectives: This study aimed to investigate the potential of transmission and heritability of carbapenemase gene (bla_KPC-2 or bla_NDM-1)-encoding or mcr-1-encoding plasmids in clinical Enterobacteriaceae strains. 
Methods: The potential of transmission of carbapenemase gene (bla_KPC-2 or bla_NDM-1)-encoding or mcr-1-encoding plasmids in clinical Enterobacteriaceae strains was tested in three conjugation models, namely the filter mating conjugation in laboratory condition, the meat product model and the GI tract of rats. The stability of plasmids in Enterobacteriaceae strains was also determined. 
Results: We demonstrated that plasmids carrying a carbapenemase gene (bla_KPC-2 or bla_NDM-1) could be efficiently conjugated to strains carrying the mcr-1 gene and vice versa, and that these plasmids could stably co-exist in clinical Enterobacteriaceae strains. These findings suggest that Enterobacteriaceae can readily acquire phenotypic resistance to both carbapenem and colistin in natural environment such as in food products and GI tracts of human and animals. 
Conclusions: Gene transfer events are common among members of Enterobacteriaceae and serve as a key mechanism that facilitates adaptation to new environment. Development of innovative strategies and surveillance measures to curtail the dissemination of multidrug resistance plasmids is necessary. Transmission and stable inheritance of these two types of plasmids would lead to the emergence of multidrug resistant pathogens that are resistant to all currently available last-line antibiotics for Gram-negative bacterial infections.