Mechanisms of blaIMP-4 dissemination across diverse carbapenem-resistant clinical isolates

ABSTRACT: Objective: The IMP-4 carbapenemase is an endemic cause of carbapenem resistance in the Asia-Pacific region. Our aim was to determine the dissemination mechanism of the blaIMP-4 gene. Methods: Twelve representative Australian IMP-4 clinical isolates from The Alfred Hospital (Victoria, Aust...

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Main Authors: Ying Fu, Faye C. Morris, Stephanie C. Pereira, Xenia Kostoulias, Yan Jiang, Callum Vidor, Galain Williams, Yogi Srikhanta, Nenad Macesic, Yunsong Yu, Dena Lyras, Anton Y. Peleg
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Journal of Global Antimicrobial Resistance
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213716525000086
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author Ying Fu
Faye C. Morris
Stephanie C. Pereira
Xenia Kostoulias
Yan Jiang
Callum Vidor
Galain Williams
Yogi Srikhanta
Nenad Macesic
Yunsong Yu
Dena Lyras
Anton Y. Peleg
author_facet Ying Fu
Faye C. Morris
Stephanie C. Pereira
Xenia Kostoulias
Yan Jiang
Callum Vidor
Galain Williams
Yogi Srikhanta
Nenad Macesic
Yunsong Yu
Dena Lyras
Anton Y. Peleg
author_sort Ying Fu
collection DOAJ
description ABSTRACT: Objective: The IMP-4 carbapenemase is an endemic cause of carbapenem resistance in the Asia-Pacific region. Our aim was to determine the dissemination mechanism of the blaIMP-4 gene. Methods: Twelve representative Australian IMP-4 clinical isolates from The Alfred Hospital (Victoria, Australia) were characterised using antimicrobial susceptibility testing, with their genome and plasmid assemblies analysed. The conjugation efficiencies of different plasmids were investigated using filter mating with four recipient strains across two species. Results: Selected IMP-4 isolates included six species and four genera (Enterobacter, Klebsiella, Serratia, and Acinetobacter), whereby isolates of the same species belonged to the same sequence type and were closely related. Four IMP-4 plasmid types were noted: IncHI2A types 1 and 2 (Klebsiella spp. and Enterobacter hormaechei, respectively), IncC (Serratia marcescens and Klebsiella pneumoniae), and a novel type in Acinetobacter pittii. Sequence homology was observed across all plasmids at the blaIMP-4 location, termed Region I, with IS26 on IncHI2A, and IS5075 and Tn3 resistance gene cassettes present on IncC plasmids. Genomic rearrangements mediated by IS26 or Tn3 and IS5075 were identified in Region I of plasmids from the same Inc type. The plasmids of each Inc type were capable of conjugative transfer with varying efficiency. IncH12A plasmids and K. pneumoniae IncC displayed higher transfer efficiencies than other plasmids examined in this study when using the recipient E. coli strain J53 (with conjugation efficiencies of 1.17×10−2 to 5.02×10−5, P < 0.001). Conclusions: Clonal spread, Inc type, homologous region, and insertion sequences are important mobility factors in the dissemination and evolution of blaIMP-4 plasmids.
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spelling doaj-art-71a67e6a9806492a8f464ae07724c56d2025-02-06T05:11:35ZengElsevierJournal of Global Antimicrobial Resistance2213-71652025-03-0141189194Mechanisms of blaIMP-4 dissemination across diverse carbapenem-resistant clinical isolatesYing Fu0Faye C. Morris1Stephanie C. Pereira2Xenia Kostoulias3Yan Jiang4Callum Vidor5Galain Williams6Yogi Srikhanta7Nenad Macesic8Yunsong Yu9Dena Lyras10Anton Y. Peleg11Department of Clinical Laboratory, Sir Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, AustraliaInfection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, AustraliaInfection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, AustraliaInfection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, Australia; Department of Infectious Diseases, Alfred Health and School of Translational Medicine, Monash University, Melbourne, Victoria, AustraliaInfection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, Australia; Department of Infectious Diseases, Sir Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, ChinaInfection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, AustraliaInfection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, AustraliaInfection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, AustraliaInfection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, Australia; Department of Infectious Diseases, Alfred Health and School of Translational Medicine, Monash University, Melbourne, Victoria, AustraliaDepartment of Clinical Laboratory, Sir Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Department of Infectious Diseases, Sir Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, ChinaInfection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, AustraliaInfection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, Australia; Department of Infectious Diseases, Alfred Health and School of Translational Medicine, Monash University, Melbourne, Victoria, Australia; Corresponding author.ABSTRACT: Objective: The IMP-4 carbapenemase is an endemic cause of carbapenem resistance in the Asia-Pacific region. Our aim was to determine the dissemination mechanism of the blaIMP-4 gene. Methods: Twelve representative Australian IMP-4 clinical isolates from The Alfred Hospital (Victoria, Australia) were characterised using antimicrobial susceptibility testing, with their genome and plasmid assemblies analysed. The conjugation efficiencies of different plasmids were investigated using filter mating with four recipient strains across two species. Results: Selected IMP-4 isolates included six species and four genera (Enterobacter, Klebsiella, Serratia, and Acinetobacter), whereby isolates of the same species belonged to the same sequence type and were closely related. Four IMP-4 plasmid types were noted: IncHI2A types 1 and 2 (Klebsiella spp. and Enterobacter hormaechei, respectively), IncC (Serratia marcescens and Klebsiella pneumoniae), and a novel type in Acinetobacter pittii. Sequence homology was observed across all plasmids at the blaIMP-4 location, termed Region I, with IS26 on IncHI2A, and IS5075 and Tn3 resistance gene cassettes present on IncC plasmids. Genomic rearrangements mediated by IS26 or Tn3 and IS5075 were identified in Region I of plasmids from the same Inc type. The plasmids of each Inc type were capable of conjugative transfer with varying efficiency. IncH12A plasmids and K. pneumoniae IncC displayed higher transfer efficiencies than other plasmids examined in this study when using the recipient E. coli strain J53 (with conjugation efficiencies of 1.17×10−2 to 5.02×10−5, P < 0.001). Conclusions: Clonal spread, Inc type, homologous region, and insertion sequences are important mobility factors in the dissemination and evolution of blaIMP-4 plasmids.http://www.sciencedirect.com/science/article/pii/S2213716525000086BlaIMP-4Species diversityPlasmid incompatibilityHomologous recombinationIS-based resistance gene cassettes
spellingShingle Ying Fu
Faye C. Morris
Stephanie C. Pereira
Xenia Kostoulias
Yan Jiang
Callum Vidor
Galain Williams
Yogi Srikhanta
Nenad Macesic
Yunsong Yu
Dena Lyras
Anton Y. Peleg
Mechanisms of blaIMP-4 dissemination across diverse carbapenem-resistant clinical isolates
Journal of Global Antimicrobial Resistance
BlaIMP-4
Species diversity
Plasmid incompatibility
Homologous recombination
IS-based resistance gene cassettes
title Mechanisms of blaIMP-4 dissemination across diverse carbapenem-resistant clinical isolates
title_full Mechanisms of blaIMP-4 dissemination across diverse carbapenem-resistant clinical isolates
title_fullStr Mechanisms of blaIMP-4 dissemination across diverse carbapenem-resistant clinical isolates
title_full_unstemmed Mechanisms of blaIMP-4 dissemination across diverse carbapenem-resistant clinical isolates
title_short Mechanisms of blaIMP-4 dissemination across diverse carbapenem-resistant clinical isolates
title_sort mechanisms of blaimp 4 dissemination across diverse carbapenem resistant clinical isolates
topic BlaIMP-4
Species diversity
Plasmid incompatibility
Homologous recombination
IS-based resistance gene cassettes
url http://www.sciencedirect.com/science/article/pii/S2213716525000086
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