Abstract
BackgroundNew Delhi metallo-β-lactamase (blaNDM), 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 blaNDM.MethodsTo investigate local transmission patterns in the context of a single hospital, whole genome sequencing data of the first 11 blaNDM-positive bacteria isolated in a local hospital were analyzed to: (1) identify and compare blaNDM-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 blaNDM-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 blaNDM-positive plasmid cluster to infer the phylogenetic relationship within each cluster; (3) gene transposition events introducing blaNDM into different plasmid backbones were identified; and (4) clustering pattern was correlated with the plasmids’ incompatibility group and geographical distribution.ResultsAnalysis of the first 11 blaNDM-positive isolates from a single hospital revealed very low blaNDM-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 blaNDM spread involved marked plasmid diversity with no predominant bacterial clone. Thirty-nine (1.4 %) out of the 2749 complete plasmid sequences were blaNDM-positive, and could be resolved into 7 clusters, which were associated with plasmid incompatibility group and geographical distribution. The blaNDM gene module was witnessed to mobilize between different plasmid backbones on at least 6 independent occasions.ConclusionsOur analysis revealed the complex genetic pathways of blaNDM spread, with global dissemination characterized mainly by transposition of the blaNDM 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 blaNDM spread.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2740-0) contains supplementary material, which is available to authorized users.
Highlights
New Delhi metallo-β-lactamase, 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
BlaNDM spread is characterized by alarming public health features, including: (1) broad Gram-negative bacterial host range, including highlyvirulent bacteria such as Vibrio cholera and Shigella boydii [12]; (2) frequent acquisition among Escherichia coli and Klebsiella pneumoniae, which are Gram-negative species carried as gut flora and able to survive in the inanimate environment; (3) widespread presence in the Indian subcontinent, Southeast and East Asia, home to a large proportion of the global human population; and (4) co-carriage with other resistance genes on the blaNDM-bearing plasmid [13]
The infection control response to a new blaNDM-positive patient detected in the course of routine testing included strict isolation of the index patient, contact tracing within the same ward and in previously admitted wards, and screening of these contacts with rectal swabs for carbapenemase-producing Enterobacteriaceae (CPE) carriage using draft guidelines issued by CDC
Summary
New Delhi metallo-β-lactamase (blaNDM), 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. BlaNDM spread is characterized by alarming public health features, including: (1) broad Gram-negative bacterial host range, including highlyvirulent bacteria such as Vibrio cholera and Shigella boydii [12]; (2) frequent acquisition among Escherichia coli and Klebsiella pneumoniae, which are Gram-negative species carried as gut flora and able to survive in the inanimate environment; (3) widespread presence in the Indian subcontinent, Southeast and East Asia, home to a large proportion of the global human population; and (4) co-carriage with other resistance genes on the blaNDM-bearing plasmid [13]
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