Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant <italic toggle="yes">Enterobacteriaceae</italic>

ABSTRACT Carbapenem-resistant Enterobacteriaceae (CRE) infections, high in morbidity and mortality, pose serious clinical challenges due to limited treatment options. A previous CRE surveillance study on 1,507 patients from 43 hospitals in Osaka, Japan, revealed that 12% of patients carried CRE and...

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Autores principales:	Ryuichiro Abe, Yukihiro Akeda, Yo Sugawara, Dan Takeuchi, Yuki Matsumoto, Daisuke Motooka, Norihisa Yamamoto, Ryuji Kawahara, Kazunori Tomono, Yuji Fujino, Shigeyuki Hamada
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Enterobacteriaceae IMP-1 IMP-6 carbapenem resistance carbapenemase chromosomal integration Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/78f66f8e3254451e99f8ecb9156b93ab
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spelling	oai:doaj.org-article:78f66f8e3254451e99f8ecb9156b93ab2021-12-02T18:15:46ZCharacterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant <italic toggle="yes">Enterobacteriaceae</italic>10.1128/mSystems.00759-202379-5077https://doaj.org/article/78f66f8e3254451e99f8ecb9156b93ab2020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00759-20https://doaj.org/toc/2379-5077ABSTRACT Carbapenem-resistant Enterobacteriaceae (CRE) infections, high in morbidity and mortality, pose serious clinical challenges due to limited treatment options. A previous CRE surveillance study on 1,507 patients from 43 hospitals in Osaka, Japan, revealed that 12% of patients carried CRE and that 95% of the CRE isolates were IMP-type carbapenemase producers. Here, the mechanisms for this regional dissemination of a single carbapenemase gene were investigated. Since the dissemination of CRE is primarily due to the transmission of carbapenemase genes located on plasmids, we analyzed the plasmidome of 230 CRE isolates carrying blaIMP by whole-genome sequencing and Southern blotting. blaIMP-6 was found to be predominantly disseminated among chromosomally distinct isolates through the pKPI-6 plasmid. Underlying the vast clonal dissemination of pKPI-6, various subpopulations deriving from pKPI-6 were identified, which had acquired advantages for the dissemination of CRE isolates. A cluster exhibiting heteroresistance against meropenem by the transcriptional regulation of blaIMP-6 caused an outbreak likely through covert transmission of blaIMP-6. For stable carriage of blaIMP-6, they occasionally integrated blaIMP-6 on their chromosomes. In addition, we detected one isolate that broadened the range of antimicrobial resistance through a single point mutation in blaIMP-6 on pKPI-6. Multifaceted analysis of the plasmidome granted us more accurate perspectives on the horizontal spread of CRE isolates, which is difficult to trace only by comparing the whole genomes. This study revealed the predominant spread of a specific carbapenemase-encoding plasmid accompanying the emergence of phenotypically diverse derivatives, which may facilitate further dissemination of CRE in various environments. IMPORTANCE Global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens human health by limiting the efficacy of antibiotics even against common bacterial infections. Carbapenem resistance, mainly due to carbapenemase, is generally encoded on plasmids and is spread across bacterial species by conjugation. Most CRE epidemiological studies have analyzed whole genomes or only contigs of CRE isolates. Here, plasmidome analysis on 230 CRE isolates carrying blaIMP was performed to shed light into the dissemination of a single carbapenemase gene in Osaka, Japan. The predominant dissemination of blaIMP-6 by the pKPI-6 plasmid among genetically distinct isolates was revealed, as well as the emergences of pKPI-6 derivatives that acquired advantages for further disseminations. Underlying vast clonal dissemination of a carbapenemase-encoding plasmid, heteroresistance was found in CRE offspring, which was generated by the transcriptional regulation of blaIMP-6, stabilization of blaIMP-6 through chromosomal integration, or broadened antimicrobial resistance due to a single point mutation in blaIMP-6.Ryuichiro AbeYukihiro AkedaYo SugawaraDan TakeuchiYuki MatsumotoDaisuke MotookaNorihisa YamamotoRyuji KawaharaKazunori TomonoYuji FujinoShigeyuki HamadaAmerican Society for MicrobiologyarticleEnterobacteriaceaeIMP-1IMP-6carbapenem resistancecarbapenemasechromosomal integrationMicrobiologyQR1-502ENmSystems, Vol 5, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Enterobacteriaceae IMP-1 IMP-6 carbapenem resistance carbapenemase chromosomal integration Microbiology QR1-502
spellingShingle	Enterobacteriaceae IMP-1 IMP-6 carbapenem resistance carbapenemase chromosomal integration Microbiology QR1-502 Ryuichiro Abe Yukihiro Akeda Yo Sugawara Dan Takeuchi Yuki Matsumoto Daisuke Motooka Norihisa Yamamoto Ryuji Kawahara Kazunori Tomono Yuji Fujino Shigeyuki Hamada Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant <italic toggle="yes">Enterobacteriaceae</italic>
description	ABSTRACT Carbapenem-resistant Enterobacteriaceae (CRE) infections, high in morbidity and mortality, pose serious clinical challenges due to limited treatment options. A previous CRE surveillance study on 1,507 patients from 43 hospitals in Osaka, Japan, revealed that 12% of patients carried CRE and that 95% of the CRE isolates were IMP-type carbapenemase producers. Here, the mechanisms for this regional dissemination of a single carbapenemase gene were investigated. Since the dissemination of CRE is primarily due to the transmission of carbapenemase genes located on plasmids, we analyzed the plasmidome of 230 CRE isolates carrying blaIMP by whole-genome sequencing and Southern blotting. blaIMP-6 was found to be predominantly disseminated among chromosomally distinct isolates through the pKPI-6 plasmid. Underlying the vast clonal dissemination of pKPI-6, various subpopulations deriving from pKPI-6 were identified, which had acquired advantages for the dissemination of CRE isolates. A cluster exhibiting heteroresistance against meropenem by the transcriptional regulation of blaIMP-6 caused an outbreak likely through covert transmission of blaIMP-6. For stable carriage of blaIMP-6, they occasionally integrated blaIMP-6 on their chromosomes. In addition, we detected one isolate that broadened the range of antimicrobial resistance through a single point mutation in blaIMP-6 on pKPI-6. Multifaceted analysis of the plasmidome granted us more accurate perspectives on the horizontal spread of CRE isolates, which is difficult to trace only by comparing the whole genomes. This study revealed the predominant spread of a specific carbapenemase-encoding plasmid accompanying the emergence of phenotypically diverse derivatives, which may facilitate further dissemination of CRE in various environments. IMPORTANCE Global dissemination of carbapenem-resistant Enterobacteriaceae (CRE) threatens human health by limiting the efficacy of antibiotics even against common bacterial infections. Carbapenem resistance, mainly due to carbapenemase, is generally encoded on plasmids and is spread across bacterial species by conjugation. Most CRE epidemiological studies have analyzed whole genomes or only contigs of CRE isolates. Here, plasmidome analysis on 230 CRE isolates carrying blaIMP was performed to shed light into the dissemination of a single carbapenemase gene in Osaka, Japan. The predominant dissemination of blaIMP-6 by the pKPI-6 plasmid among genetically distinct isolates was revealed, as well as the emergences of pKPI-6 derivatives that acquired advantages for further disseminations. Underlying vast clonal dissemination of a carbapenemase-encoding plasmid, heteroresistance was found in CRE offspring, which was generated by the transcriptional regulation of blaIMP-6, stabilization of blaIMP-6 through chromosomal integration, or broadened antimicrobial resistance due to a single point mutation in blaIMP-6.
format	article
author	Ryuichiro Abe Yukihiro Akeda Yo Sugawara Dan Takeuchi Yuki Matsumoto Daisuke Motooka Norihisa Yamamoto Ryuji Kawahara Kazunori Tomono Yuji Fujino Shigeyuki Hamada
author_facet	Ryuichiro Abe Yukihiro Akeda Yo Sugawara Dan Takeuchi Yuki Matsumoto Daisuke Motooka Norihisa Yamamoto Ryuji Kawahara Kazunori Tomono Yuji Fujino Shigeyuki Hamada
author_sort	Ryuichiro Abe
title	Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant <italic toggle="yes">Enterobacteriaceae</italic>
title_short	Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant <italic toggle="yes">Enterobacteriaceae</italic>
title_full	Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant <italic toggle="yes">Enterobacteriaceae</italic>
title_fullStr	Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant <italic toggle="yes">Enterobacteriaceae</italic>
title_full_unstemmed	Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant <italic toggle="yes">Enterobacteriaceae</italic>
title_sort	characterization of the plasmidome encoding carbapenemase and mechanisms for dissemination of carbapenem-resistant <italic toggle="yes">enterobacteriaceae</italic>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/78f66f8e3254451e99f8ecb9156b93ab
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Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant <italic toggle="yes">Enterobacteriaceae</italic>

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