Mechanisms Involved in Acquisition of blaNDM Genes by IncA/C2 and IncFIIY Plasmids.
blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family.
The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia alexander.wailan@uqconnect.edu.au sally.partridge@health.nsw.gov.au.
Alexander M
AM
Wailan
The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.
Hanna E
HE
Sidjabat
The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.
Wan Keat
WK
Yam
Australian Infectious Diseases Research Centre, Brisbane, Australia.
Nabil-Fareed
NF
Alikhan
Australian Infectious Diseases Research Centre, Brisbane, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Nicola K
NK
Petty
The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.
Anna L
AL
Sartor
Institute of Environmental Science and Research, Wellington, New Zealand.
Deborah A
DA
Williamson
Australian Infectious Diseases Research Centre, Brisbane, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Brian M
BM
Forde
Australian Infectious Diseases Research Centre, Brisbane, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Mark A
0000-0003-4863-9260
MA
Schembri
Australian Infectious Diseases Research Centre, Brisbane, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Scott A
SA
Beatson
Australian Infectious Diseases Research Centre, Brisbane, Australia Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, Australia Pathology Queensland, Brisbane, Australia.
David L
DL
Paterson
The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.
Timothy R
TR
Walsh
Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney, Westmead Hospital, New South Wales, Australia alexander.wailan@uqconnect.edu.au sally.partridge@health.nsw.gov.au.
Sally R
SR
Partridge
D000150:Acinetobacter / Q000187:drug effects / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015780:Carbapenems / Q000494:pharmacology; D004251:DNA Transposable Elements / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D016972:Enterobacter cloacae / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000235:genetics*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004251:DNA Transposable Elements; D012336:RNA, Ribosomal, 16S; D001618:beta-Lactamases