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2016 ; 17
(ไ): 452
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Local transmission and global dissemination of New Delhi Metallo-Beta-Lactamase
(NDM): a whole genome analysis
#MMPMID27297071
Khong WX
; Xia E
; Marimuthu K
; Xu W
; Teo YY
; Tan EL
; Neo S
; Krishnan PU
; Ang BS
; Lye DC
; Chow AL
; Ong RT
; Ng OT
BMC Genomics
2016[Jun]; 17
(ไ): 452
PMID27297071
show ga
BACKGROUND: New Delhi metallo-?-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.