Mechanisms of blaIMP-4 dissemination across diverse carbapenem-resistant clinical isolates
Ying Fu1, Faye C Morris2, Stephanie C Pereira2
1Department 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, Australia.
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.
Insights
The blaIMP-4 gene spreads via plasmids in Australian hospitals. Clonal spread, plasmid type, and insertion sequences are key factors in its dissemination and evolution.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Carbapenem resistance poses a significant global health threat.
- The IMP-4 carbapenemase is a major driver of carbapenem resistance in the Asia-Pacific region.
- Understanding the dissemination mechanisms of carbapenemase genes is crucial for effective control strategies.
Purpose of the Study:
- To investigate the dissemination mechanisms of the blaIMP-4 gene in Australia.
- To characterize the genomic and plasmid features of IMP-4 carbapenemase-producing clinical isolates.
- To assess the conjugative transfer efficiency of different IMP-4-carrying plasmids.
Main Methods:
- Antimicrobial susceptibility testing of 12 Australian IMP-4 clinical isolates.
- Whole-genome sequencing and plasmid assembly analysis.
- Conjugation experiments using filter mating with multiple recipient strains.
Main Results:
- IMP-4 isolates comprised six species across four genera, with closely related isolates within the same species.
- Four IMP-4 plasmid types were identified: IncHI2A (types 1 and 2), IncC, and a novel type.
- Sequence homology at the blaIMP-4 locus (Region I) was observed across plasmids, involving insertion sequences (IS26, IS5075) and Tn3.
- Plasmids exhibited varying conjugative transfer efficiencies, with IncHI2A and K. pneumoniae IncC showing higher rates.
Conclusions:
- Clonal spread plays a role in the dissemination of IMP-4.
- Plasmid Inc type, homologous regions, and insertion sequences are critical for blaIMP-4 mobility and evolution.
- These factors contribute to the adaptability and spread of carbapenem resistance.
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