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

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

doi:10.1016/j.jgar.2025.01.003

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

J Glob Antimicrob Resist. 2025 Jan 16:S2213-7165(25)00008-6. doi: 10.1016/j.jgar.2025.01.003. Online ahead of print.

Authors

Affiliations

¹ Department of Clinical Laboratory, Sir Run 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.
² Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton Victoria, Australia; Centre to Impact AMR, Monash University, Clayton, Victoria, Australia.
³ Infection 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.
⁴ Infection 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 Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
⁵ Department of Clinical Laboratory, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
⁶ Infection 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. Electronic address: [email protected].

PMID: 39826686
DOI: 10.1016/j.jgar.2025.01.003

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 bla_IMP-4 gene.

Methods: Twelve representative Australian IMP-4 clinical isolates from The Alfred Hospital, were characterised using antimicrobial susceptibility testing and genome and plasmid assemblies analysed. 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 type 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 bla_IMP-4 location, termed Region I, with IS26- on IncHI2A and IS5075-and Tn3 resistance gene cassettes present IncC plasmids, respectively. Genomic rearrangements mediated by IS26 or Tn3 and IS5075 were identified in Region I of plasmids from the same Inc type. 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 - 5.02×10^-5, p<0.001).

Conclusion: Clonal spread, Inc type, homologous region and insertion sequences are important mobility factors in the dissemination and evolution of bla_IMP-4 plasmids.

Keywords: IS based resistance gene cassettes; bla(IMP-4); homologous recombination; plasmid incompatibility; species diversity.