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Patrice Nordmann - One of the best experts on this subject based on the ideXlab platform.
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Genetic Features of the Widespread Plasmid Coding for the
2016Co-Authors: Carbapenemase Oxa, Laurent Poirel, Remy A Bonnin, Patrice NordmannAbstract:Complete sequencing of plasmid pOXA-48a carrying the blaOXA-48 gene from a Klebsiella pneumoniae isolate was performed. Its backbone corresponded to that of an IncL/M-type plasmid, in which the blaOXA-48 gene had been integrated through the acquisi-tion of the Tn1999 Composite Transposon without any other antibiotic resistance gene. Molecular epidemiology using a collec-tion of international OXA-48 producers revealed the wide diffusion of pOXA-48a or closely related plasmids. Carbapenem-hydrolyzing -lactamases belonging to Amblerclasses A, B, and D have been found worldwide among the Enterobacteriaceae (24). Although carbapenem-hydrolyzing class D -lactamases (CHDLs) are identified mainly in Acinetobacter species (19, 23), OXA-48 has been identified only in the Entero-bacteriaceae. The blaOXA-48 gene was first identified in a Klebsiella pneumoniae isolate from Turkey (22). Since then, several other OXA-48-producing isolates of various enterobacterial species (in-cluding Citrobacter freundii and Escherichia coli) have been re
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derepressed transfer properties leading to the efficient spread of the plasmid encoding carbapenemase oxa 48
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Anais Potron, Laurent Poirel, Patrice NordmannAbstract:The current emergence of the carbapenemase OXA-48 among Enterobacteriaceae is related to the spread of a single IncL/M-type plasmid, pOXA-48a. This plasmid harbors the blaOXA-48 gene within a Composite Transposon, Tn1999, which is inserted into the tir gene, encoding a transfer inhibition protein. We showed that the insertion of Tn1999 into the tir gene was involved in a higher transfer frequency of plasmid pOXA-48a. This may likely be the key factor for the successful dissemination of this plasmid.
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tn125 related acquisition of blandm like genes in acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2012Co-Authors: Laurent Poirel, Remy A Bonnin, Anne Boulanger, Jacques Schrenzel, Martin Kaase, Patrice NordmannAbstract:A multidrug-resistant Acinetobacter baumannii isolate recovered from a patient hospitalized in Switzerland after a transfer from Serbia produced the NDM-1 carbapenemase. The bla(NDM-1) gene was part of a chromosomally located Tn125 Composite Transposon bracketed by two copies of the same insertion sequence, ISAba125. This Transposon was also associated with the acquisition and expression of the bla(NDM-2) gene in an A. baumannii isolate in Germany. Tn125 appears to be the main vehicle for dissemination of bla(NDM) genes in that species.
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genetic features of the widespread plasmid coding for the carbapenemase oxa 48
Antimicrobial Agents and Chemotherapy, 2012Co-Authors: Laurent Poirel, Remy A Bonnin, Patrice NordmannAbstract:Complete sequencing of plasmid pOXA-48a carrying the blaOXA-48 gene from a Klebsiella pneumoniae isolate was performed. Its backbone corresponded to that of an IncL/M-type plasmid, in which the blaOXA-48 gene had been integrated through the acquisition of the Tn1999 Composite Transposon without any other antibiotic resistance gene. Molecular epidemiology using a collection of international OXA-48 producers revealed the wide diffusion of pOXA-48a or closely related plasmids.
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functional analysis of insertion sequence isaba1 responsible for genomic plasticity of acinetobacter baumannii
Journal of Bacteriology, 2009Co-Authors: Pauline D Mugnier, Laurent Poirel, Patrice NordmannAbstract:ISAba1 is an insertion sequence that is widely distributed in Acinetobacter baumannii. We demonstrated here that ISAba1 and the Composite Transposon Tn2006 are capable of transposition, generating 9-bp target site duplications. The expression of the ISAba1 transposase-encoding gene was downregulated by translational frameshifting.
Laurent Poirel - One of the best experts on this subject based on the ideXlab platform.
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Genetic Features of the Widespread Plasmid Coding for the
2016Co-Authors: Carbapenemase Oxa, Laurent Poirel, Remy A Bonnin, Patrice NordmannAbstract:Complete sequencing of plasmid pOXA-48a carrying the blaOXA-48 gene from a Klebsiella pneumoniae isolate was performed. Its backbone corresponded to that of an IncL/M-type plasmid, in which the blaOXA-48 gene had been integrated through the acquisi-tion of the Tn1999 Composite Transposon without any other antibiotic resistance gene. Molecular epidemiology using a collec-tion of international OXA-48 producers revealed the wide diffusion of pOXA-48a or closely related plasmids. Carbapenem-hydrolyzing -lactamases belonging to Amblerclasses A, B, and D have been found worldwide among the Enterobacteriaceae (24). Although carbapenem-hydrolyzing class D -lactamases (CHDLs) are identified mainly in Acinetobacter species (19, 23), OXA-48 has been identified only in the Entero-bacteriaceae. The blaOXA-48 gene was first identified in a Klebsiella pneumoniae isolate from Turkey (22). Since then, several other OXA-48-producing isolates of various enterobacterial species (in-cluding Citrobacter freundii and Escherichia coli) have been re
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derepressed transfer properties leading to the efficient spread of the plasmid encoding carbapenemase oxa 48
Antimicrobial Agents and Chemotherapy, 2014Co-Authors: Anais Potron, Laurent Poirel, Patrice NordmannAbstract:The current emergence of the carbapenemase OXA-48 among Enterobacteriaceae is related to the spread of a single IncL/M-type plasmid, pOXA-48a. This plasmid harbors the blaOXA-48 gene within a Composite Transposon, Tn1999, which is inserted into the tir gene, encoding a transfer inhibition protein. We showed that the insertion of Tn1999 into the tir gene was involved in a higher transfer frequency of plasmid pOXA-48a. This may likely be the key factor for the successful dissemination of this plasmid.
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tn125 related acquisition of blandm like genes in acinetobacter baumannii
Antimicrobial Agents and Chemotherapy, 2012Co-Authors: Laurent Poirel, Remy A Bonnin, Anne Boulanger, Jacques Schrenzel, Martin Kaase, Patrice NordmannAbstract:A multidrug-resistant Acinetobacter baumannii isolate recovered from a patient hospitalized in Switzerland after a transfer from Serbia produced the NDM-1 carbapenemase. The bla(NDM-1) gene was part of a chromosomally located Tn125 Composite Transposon bracketed by two copies of the same insertion sequence, ISAba125. This Transposon was also associated with the acquisition and expression of the bla(NDM-2) gene in an A. baumannii isolate in Germany. Tn125 appears to be the main vehicle for dissemination of bla(NDM) genes in that species.
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genetic features of the widespread plasmid coding for the carbapenemase oxa 48
Antimicrobial Agents and Chemotherapy, 2012Co-Authors: Laurent Poirel, Remy A Bonnin, Patrice NordmannAbstract:Complete sequencing of plasmid pOXA-48a carrying the blaOXA-48 gene from a Klebsiella pneumoniae isolate was performed. Its backbone corresponded to that of an IncL/M-type plasmid, in which the blaOXA-48 gene had been integrated through the acquisition of the Tn1999 Composite Transposon without any other antibiotic resistance gene. Molecular epidemiology using a collection of international OXA-48 producers revealed the wide diffusion of pOXA-48a or closely related plasmids.
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functional analysis of insertion sequence isaba1 responsible for genomic plasticity of acinetobacter baumannii
Journal of Bacteriology, 2009Co-Authors: Pauline D Mugnier, Laurent Poirel, Patrice NordmannAbstract:ISAba1 is an insertion sequence that is widely distributed in Acinetobacter baumannii. We demonstrated here that ISAba1 and the Composite Transposon Tn2006 are capable of transposition, generating 9-bp target site duplications. The expression of the ISAba1 transposase-encoding gene was downregulated by translational frameshifting.
Michael Chandler - One of the best experts on this subject based on the ideXlab platform.
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the birth and demise of the isapl1 mcr 1 isapl1 Composite Transposon the vehicle for transferable colistin resistance
Mbio, 2018Co-Authors: Erik Snesrud, Patrick Mcgann, Michael ChandlerAbstract:ABSTRACT The origin and mobilization of the ~2,609-bp DNA segment containing the mobile colistin resistance gene mcr-1 continue to be sources of uncertainty, but recent evidence suggests that the gene originated in Moraxella species. Moreover mcr-1 can be mobilized as an ISApl1-flanked Composite Transposon (Tn6330), but many sequences have been identified without ISApl1 or with just a single copy (single ended). To further clarify the origins and mobilization of mcr-1, we employed the Geneious R8 software suite to comprehensively analyze the genetic environment of every complete mcr-1 structure deposited in GenBank as of this writing (September 2017) both with and without associated ISApl1 (n = 273). This revealed that the 2,609-bp mcr-1 structure was likely mobilized from a close relative of a novel species of Moraxella containing a chromosomal region sharing >96% nucleotide identity with the canonical sequence. This chromosomal region is bounded by AT and CG dinucleotides, which have been described on the inside ends (IE) of all intact Tn6330 described to date and represent the ancestral 2-bp target site duplications (TSDs) generated by ISApl1 transposition. We further demonstrate that all mcr-1 structures with just one ISApl1 copy or with no ISApl1 copies were formed by deletion of ISApl1 from the ancestral Tn6330, likely by a process related to the “copy-out–paste-in” transposition mechanism. Finally, we show that only the rare examples of single-ended structures that have retained a portion of the excised downstream ISApl1 including the entire inverted right repeat might be capable of mobilization. IMPORTANCE A comprehensive analysis of all intact mcr-1 sequences in GenBank was used to identify a region on the chromosome of a novel Moraxella species with remarkable homology to the canonical mcr-1 structure and that likely represents the origin of this important gene. These data also demonstrate that all mcr-1 structures lacking one or both flanking ISApl1 were formed from ancestral Composite Transposons that subsequently lost the insertion sequences by a process of abortive transposition. This observation conclusively shows that mobilization of mcr-1 occurs as part of a Composite Transposon and that structures lacking the downstream ISApl1 are not capable of mobilization.
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The Birth and Demise of the ISApl1-mcr-1-ISApl1 Composite Transposon: the Vehicle for Transferable Colistin Resistance
American Society for Microbiology, 2018Co-Authors: Erik Snesrud, Patrick Mcgann, Michael Chandler, Richard P. NovickAbstract:The origin and mobilization of the ~2,609-bp DNA segment containing the mobile colistin resistance gene mcr-1 continue to be sources of uncertainty, but recent evidence suggests that the gene originated in Moraxella species. Moreover mcr-1 can be mobilized as an ISApl1-flanked Composite Transposon (Tn6330), but many sequences have been identified without ISApl1 or with just a single copy (single ended). To further clarify the origins and mobilization of mcr-1, we employed the Geneious R8 software suite to comprehensively analyze the genetic environment of every complete mcr-1 structure deposited in GenBank as of this writing (September 2017) both with and without associated ISApl1 (n = 273). This revealed that the 2,609-bp mcr-1 structure was likely mobilized from a close relative of a novel species of Moraxella containing a chromosomal region sharing >96% nucleotide identity with the canonical sequence. This chromosomal region is bounded by AT and CG dinucleotides, which have been described on the inside ends (IE) of all intact Tn6330 described to date and represent the ancestral 2-bp target site duplications (TSDs) generated by ISApl1 transposition. We further demonstrate that all mcr-1 structures with just one ISApl1 copy or with no ISApl1 copies were formed by deletion of ISApl1 from the ancestral Tn6330, likely by a process related to the “copy-out–paste-in” transposition mechanism. Finally, we show that only the rare examples of single-ended structures that have retained a portion of the excised downstream ISApl1 including the entire inverted right repeat might be capable of mobilization
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a model for transposition of the colistin resistance gene mcr 1 by isapl1
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Erik Snesrud, Patrick Mcgann, Michael Chandler, Susu He, John P Dekker, Alison B Hickman, Fred DydaAbstract:ABSTRACT Analysis of mcr-1 -containing sequences identified a common ∼2,607-bp DNA segment that in many cases is flanked on one or both ends by IS Apl1 . We present evidence that mcr-1 is mobilized by an IS Apl1 Composite Transposon which has, in some cases, subsequently lost one or both copies of IS Apl1 . We also show that mcr-1 can be mobilized in some circumstances by a single upstream copy of IS Apl1 in conjunction with the remnants of a downstream IS Apl1 .
Erik Snesrud - One of the best experts on this subject based on the ideXlab platform.
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the birth and demise of the isapl1 mcr 1 isapl1 Composite Transposon the vehicle for transferable colistin resistance
Mbio, 2018Co-Authors: Erik Snesrud, Patrick Mcgann, Michael ChandlerAbstract:ABSTRACT The origin and mobilization of the ~2,609-bp DNA segment containing the mobile colistin resistance gene mcr-1 continue to be sources of uncertainty, but recent evidence suggests that the gene originated in Moraxella species. Moreover mcr-1 can be mobilized as an ISApl1-flanked Composite Transposon (Tn6330), but many sequences have been identified without ISApl1 or with just a single copy (single ended). To further clarify the origins and mobilization of mcr-1, we employed the Geneious R8 software suite to comprehensively analyze the genetic environment of every complete mcr-1 structure deposited in GenBank as of this writing (September 2017) both with and without associated ISApl1 (n = 273). This revealed that the 2,609-bp mcr-1 structure was likely mobilized from a close relative of a novel species of Moraxella containing a chromosomal region sharing >96% nucleotide identity with the canonical sequence. This chromosomal region is bounded by AT and CG dinucleotides, which have been described on the inside ends (IE) of all intact Tn6330 described to date and represent the ancestral 2-bp target site duplications (TSDs) generated by ISApl1 transposition. We further demonstrate that all mcr-1 structures with just one ISApl1 copy or with no ISApl1 copies were formed by deletion of ISApl1 from the ancestral Tn6330, likely by a process related to the “copy-out–paste-in” transposition mechanism. Finally, we show that only the rare examples of single-ended structures that have retained a portion of the excised downstream ISApl1 including the entire inverted right repeat might be capable of mobilization. IMPORTANCE A comprehensive analysis of all intact mcr-1 sequences in GenBank was used to identify a region on the chromosome of a novel Moraxella species with remarkable homology to the canonical mcr-1 structure and that likely represents the origin of this important gene. These data also demonstrate that all mcr-1 structures lacking one or both flanking ISApl1 were formed from ancestral Composite Transposons that subsequently lost the insertion sequences by a process of abortive transposition. This observation conclusively shows that mobilization of mcr-1 occurs as part of a Composite Transposon and that structures lacking the downstream ISApl1 are not capable of mobilization.
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The Birth and Demise of the ISApl1-mcr-1-ISApl1 Composite Transposon: the Vehicle for Transferable Colistin Resistance
American Society for Microbiology, 2018Co-Authors: Erik Snesrud, Patrick Mcgann, Michael Chandler, Richard P. NovickAbstract:The origin and mobilization of the ~2,609-bp DNA segment containing the mobile colistin resistance gene mcr-1 continue to be sources of uncertainty, but recent evidence suggests that the gene originated in Moraxella species. Moreover mcr-1 can be mobilized as an ISApl1-flanked Composite Transposon (Tn6330), but many sequences have been identified without ISApl1 or with just a single copy (single ended). To further clarify the origins and mobilization of mcr-1, we employed the Geneious R8 software suite to comprehensively analyze the genetic environment of every complete mcr-1 structure deposited in GenBank as of this writing (September 2017) both with and without associated ISApl1 (n = 273). This revealed that the 2,609-bp mcr-1 structure was likely mobilized from a close relative of a novel species of Moraxella containing a chromosomal region sharing >96% nucleotide identity with the canonical sequence. This chromosomal region is bounded by AT and CG dinucleotides, which have been described on the inside ends (IE) of all intact Tn6330 described to date and represent the ancestral 2-bp target site duplications (TSDs) generated by ISApl1 transposition. We further demonstrate that all mcr-1 structures with just one ISApl1 copy or with no ISApl1 copies were formed by deletion of ISApl1 from the ancestral Tn6330, likely by a process related to the “copy-out–paste-in” transposition mechanism. Finally, we show that only the rare examples of single-ended structures that have retained a portion of the excised downstream ISApl1 including the entire inverted right repeat might be capable of mobilization
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a model for transposition of the colistin resistance gene mcr 1 by isapl1
Antimicrobial Agents and Chemotherapy, 2016Co-Authors: Erik Snesrud, Patrick Mcgann, Michael Chandler, Susu He, John P Dekker, Alison B Hickman, Fred DydaAbstract:ABSTRACT Analysis of mcr-1 -containing sequences identified a common ∼2,607-bp DNA segment that in many cases is flanked on one or both ends by IS Apl1 . We present evidence that mcr-1 is mobilized by an IS Apl1 Composite Transposon which has, in some cases, subsequently lost one or both copies of IS Apl1 . We also show that mcr-1 can be mobilized in some circumstances by a single upstream copy of IS Apl1 in conjunction with the remnants of a downstream IS Apl1 .
Hongbin Song - One of the best experts on this subject based on the ideXlab platform.
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transferable plasmid borne mcr 1 in a colistin resistant shigella flexneri isolate
Applied and Environmental Microbiology, 2018Co-Authors: Beibei Liang, Adam P Roberts, Chaojie Yang, Xiaoxia Yang, Jinyan Wang, Shaofu Qiu, Hongbin SongAbstract:ABSTRACT Since the initial discovery of mcr-1 in an Escherichia coli isolate from China, the gene has also been detected in Klebsiella pneumoniae and Salmonella enterica but is rarely reported in other Enterobacteriaceae. Here, we report the isolation and identification of a Shigella flexneri strain harboring mcr-1 from stool samples in a pig farm in China from 2009. The MIC of colistin for the isolate is 4 μg/ml. Conjugation assays showed that the donor S. flexneri strain has functional and transferable colistin resistance. Sequencing revealed that mcr-1 was present on a putative Composite Transposon flanked by inverted repeats of ISApl1. IMPORTANCE There are four species of Shigella, and Shigella flexneri is the most frequently isolated species in low- and middle-income countries (LMICs). In this study, we report a functional, transferable, plasmid-mediated mcr-1 gene in S. flexneri. We have shown that mcr-1 is located on a novel Composite Transposon which is flanked by inverted repeats of ISApl1. The host strain is multidrug resistant, and this multidrug resistance is also transferable. The finding of a functional mcr-1 gene in S. flexneri, a human-associated Enterobacteriaceae family member, is a cause for concern as infections due to S. flexneri are the main Shigella infections in most low- and middle-income countries.