Local transmission and global dissemination of New Delhi Metallo-Beta-Lactamase (NDM): a whole genome analysis

BACKGROUND: New Delhi metallo-β-lactamase (bla(NDM)), a plasmid-borne carbapenemase gene associated with significant mortality and severely limited treatment options, is of global public health concern as it is found in extremely diverse Gram-negative bacterial strains. This study thus aims to genetically characterize local and global spread of bla(NDM). METHODS: To investigate local transmission patterns in the context of a single hospital, whole genome sequencing data of the first 11 bla(NDM)-positive bacteria isolated in a local hospital were analyzed to: (1) identify and compare bla(NDM)-positive plasmids; and (2) study the phylogenetic relationship of the bacteria chromosomes. The global analysis was conducted by analyzing 2749 complete plasmid sequences (including 39 bla(NDM)-positive plasmids) in the NCBI database, where: (1) the plasmids were clustered based on their gene composition similarity; (2) phylogenetic study was conducted for each bla(NDM)-positive plasmid cluster to infer the phylogenetic relationship within each cluster; (3) gene transposition events introducing bla(NDM) into different plasmid backbones were identified; and (4) clustering pattern was correlated with the plasmids’ incompatibility group and geographical distribution. RESULTS: Analysis of the first 11 bla(NDM)-positive isolates from a single hospital revealed very low bla(NDM)-positive plasmid diversity. Local transmission was characterized by clonal spread of a predominant plasmid with 2 sporadic instances of plasmid introduction. In contrast to the low diversity locally, global bla(NDM) spread involved marked plasmid diversity with no predominant bacterial clone. Thirty-nine (1.4 %) out of the 2749 complete plasmid sequences were bla(NDM)-positive, and could be resolved into 7 clusters, which were associated with plasmid incompatibility group and geographical distribution. The bla(NDM) gene module was witnessed to mobilize between different plasmid backbones on at least 6 independent occasions. CONCLUSIONS: Our analysis revealed the complex genetic pathways of bla(NDM) spread, with global dissemination characterized mainly by transposition of the bla(NDM) gene cassette into varied plasmids. Early local transmission following plasmid introduction is characterized by plasmid conjugation and bacterial spread. Our findings emphasize the importance of plasmid molecular epidemiology in understanding bla(NDM) spread. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2740-0) contains supplementary material, which is available to authorized users.