Genomic Epidemiology Insights on NDM-Producing Pathogens Revealed the Pivotal Role of Plasmids on Transmission.

Incidences of nosocomial infections mediated by New Delhi metallo-β-lactamase (NDM) enzyme-producing are increasing globally, resulting in a great burden to public health. The carbapenem-resistant (CRE) were collected from Henan, China during 2013-2016. The -positive strains were characterized using PCR, antimicrobial susceptibility testing, conjugation assay, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot, whole-genome sequencing (WGS), and bioinformatics analysis. Eighty-one NDM-producing strains were identified among 391 nonduplicate CRE strains. Among them, four strains cocarried and genes, and two carried and genes. The coexistence of and in Enterobacter hormaechei was found for the first time. In total, four subtypes were identified. Among them, and were predominant. There was an obvious increasing trend in from 2013 to 2016. Thirteen different bacterial species were found among the 81 strains, and Escherichia coli was the dominant strain. genes were located on nine different Inc-type plasmids, most of them on the IncX3 plasmids, except for the Pr-15-2-50 strain, which was located on the chromosome. We characterized two novel plasmids: the IncHI5-like plasmid carrying found in , and the IncI1 -positive plasmid. These findings provide the genomic basis for the widespread transmission of and pave the way for the formulation of more effective monitoring and control methods. To control the emergence and transmission of CRE, it is important to perform retrospective genomic investigations. It is important to evaluate the plasmid diversity, genetic environment, and evolutionary relationships of the -positive clinical strains in the early transmission stages. This study conducted an in-depth analysis of -positive pathogens during a 4-year period using different methods for observing the high prevalence and active transmission of -positive CRE. Moreover, we also explored the coexistence of the and a clinically important mobile colistin resistance gene. This study shows that the prevalence of -positive pathogens in Henan is high and the isolation rates increase each year. Moreover, plasmid-mediated horizontal transfer plays an important role in dissemination. The co-occurrence of multiple resistance genes highlighted a long-lasting evolutionary pathway. Therefore, we have suggested the long-term continuous surveillance of clinical pathogens carrying to learn the future transmission trend and curb the public health risk caused by CRE.