Genomic investigation of NDM-1 producing Enterobacterales transmission in a South Korean hospital

Abstract

Objective: Prolonged detection of multispecies New Delhi metallo-β-lactamase (NDM)-1-producing Enterobacterales was observed in front of a South Korean hospital. This study aimed to investigate the transmission mechanisms of blaNDM-1 and assess the role of environmental reservoirs in its persistence. Methods: Epidemiological data were collected, and antibiotic susceptibility testing, carbapenemases detection, and whole-genome sequencing were performed on 42 clinical and 13 environmental isolates collected between November 2018 and February 2021, during the pre-outbreak, outbreak (July–September 2019), and post-outbreak periods. Long-read complete-genome sequencing was performed on four clinical and four environmental isolates to characterize plasmids carrying blaNDM-1 and associated mobile genetic elements. Phylogenetic analyses were also performed. Results: blaNDM-1 was detected in 15 different species across clinical and environmental isolates. During the 2019 outbreak, clonal spread of Klebsiella pneumoniae and Klebsiella quasipneumoniae in the hospital was the primary mechanism of dissemination. During the post-outbreak period, horizontal gene transfer, mediated by the IncX3 plasmid carrying blaNDM-1, was the dominant transmission mechanism. This plasmid, detected in both clinical and environmental isolates, showed high genetic conservation with IncX3 plasmids reported worldwide. These plasmids contained conserved mobile genetic elements, including the IS26-dsbD-trpF-ble-blaNDM-1 structure. Conclusions: This study highlights the dual roles of clonal spread and plasmid-mediated horizontal gene transfer in the dissemination of blaNDM-1 in hospital settings. The persistence of highly conserved IncX3 plasmids in environmental isolates underscores the complexity of carbapenem resistance control. Comprehensive infection control strategies targeting patient-to-patient transmission and environmental reservoirs are crucial for mitigating the spread of NDM-producing Enterobacterales.

Keywords

• Carbapenemase-producing Enterobacterales
• New Delhi metallo-β-lactamase
• Mobile genetic element
• IncX plasmid
• horizontal gene transfer