Phenotypic and Genetic Characteristics of blaIMP-6-Harboring Enterobacterales Isolates Lacking blaCTX-M-2 in Japan

Koichi Yamaguchi1, Ryuichi Nakano1, Akiyo Nakano1

  • 1Department of Microbiology and Infectious Diseases, Nara Medical University, 840 Shijo-cho, Kashihara-shi 6348521, Nara, Japan.

Insights

Carbapenemase-producing Enterobacterales (CPE) carrying IMP-6 carbapenemase can exist without CTX-M-2 ESBL. These strains often harbor IMP-6 on diverse, non-transferable plasmids, suggesting different spread mechanisms.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Carbapenemase-producing Enterobacterales (CPE) represent a significant global health threat.
  • IMP-6 carbapenemase is prevalent in western Japan, often co-occurring with CTX-M-2 extended-spectrum beta-lactamase (ESBL).
  • The prevalence and characteristics of Enterobacterales harboring blaIMP-6 without blaCTX-M-2 are not well understood.

Purpose of the Study:

  • To investigate the phenotypic and genetic features of clinical Enterobacterales isolates carrying blaIMP-6.
  • To specifically focus on isolates lacking the blaCTX-M-2 gene.
  • To understand the plasmid context and transferability of blaIMP-6 in the absence of blaCTX-M-2.

Main Methods:

  • Antimicrobial susceptibility testing of 220 blaIMP-6-harboring Enterobacterales isolates from 76 Japanese hospitals (2014-2021).
  • Detection of CTX-M-type ESBLs, plasmid incompatibility analysis, and plasmid transfer experiments.
  • Genome sequencing and analysis to characterize genetic elements and plasmid structures.

Main Results:

  • Most isolates (203/220) co-harbored blaCTX-M-2, showing high transfer frequency and broad-spectrum resistance.
  • Seventeen isolates lacked blaCTX-M-2; nine lacked all blaCTX-M genes, while eight harbored other blaCTX-M groups.
  • Eleven isolates possessed nontransferable plasmids distinct from blaIMP-6/blaCTX-M-2 co-encoding plasmids; 15 carried only blaIMP-6 plasmids.

Conclusions:

  • blaIMP-6 can be present in Enterobacterales without blaCTX-M-2, often on diverse and nontransferable plasmids.
  • These distinct plasmid types suggest alternative, potentially slower dissemination pathways compared to epidemic strains.
  • Previously overlooked plasmids carrying blaIMP-6 warrant close monitoring due to their potential role in resistance spread.