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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-12-01
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| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSystems.00759-20 |
| _version_ | 1818733828101898240 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T23:55:40Z |
| format | Article |
| id | doaj.art-78f66f8e3254451e99f8ecb9156b93ab |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-12-17T23:55:40Z |
| publishDate | 2020-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-78f66f8e3254451e99f8ecb9156b93ab2022-12-21T21:28:05ZengAmerican Society for MicrobiologymSystems2379-50772020-12-015610.1128/mSystems.00759-20Characterization of the Plasmidome Encoding Carbapenemase and Mechanisms for Dissemination of Carbapenem-Resistant <italic toggle="yes">Enterobacteriaceae</italic>Ryuichiro Abe0Yukihiro Akeda1Yo Sugawara2Dan Takeuchi3Yuki Matsumoto4Daisuke Motooka5Norihisa Yamamoto6Ryuji Kawahara7Kazunori Tomono8Yuji Fujino9Shigeyuki Hamada10Japan-Thailand Research Collaboration Centre on Emerging and Re-emerging Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanJapan-Thailand Research Collaboration Centre on Emerging and Re-emerging Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanJapan-Thailand Research Collaboration Centre on Emerging and Re-emerging Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanJapan-Thailand Research Collaboration Centre on Emerging and Re-emerging Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanDepartment of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanDepartment of Infection Metagenomics, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanJapan-Thailand Research Collaboration Centre on Emerging and Re-emerging Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanDepartment of Microbiology, Osaka Institute of Public Health, Osaka, JapanDivision of Infection Control and Prevention, Osaka University Hospital, Osaka, JapanDepartment of Anaesthesiology and Intensive Care Medicine, Graduate School of Medicine, Osaka University, Osaka, JapanJapan-Thailand Research Collaboration Centre on Emerging and Re-emerging Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, JapanABSTRACT 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.https://journals.asm.org/doi/10.1128/mSystems.00759-20EnterobacteriaceaeIMP-1IMP-6carbapenem resistancecarbapenemasechromosomal integration |
| spellingShingle | 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> mSystems Enterobacteriaceae IMP-1 IMP-6 carbapenem resistance carbapenemase chromosomal integration |
| title | 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_short | 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 |
| topic | Enterobacteriaceae IMP-1 IMP-6 carbapenem resistance carbapenemase chromosomal integration |
| url | https://journals.asm.org/doi/10.1128/mSystems.00759-20 |
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