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Updated: Sep 14, 2025

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance

Published on: May 2, 2018

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Evolution of XDR Pseudomonas aeruginosa ST463 strains with two plasmids harboring multiple antimicrobial resistance

Yinfei Fang1, Meijun Song2,3, Yisha Zhang2,4,5

  • 1Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China.

Antimicrobial Agents and Chemotherapy
|July 23, 2025
PubMed

Insights

Extensively drug-resistant Pseudomonas aeruginosa ST463 strains carry two plasmids, including an IncP-2 megaplasmid with a Tn1403-like transposon. This transposon evolves via ISCR1 modules, leading to novel multidrug resistance mechanisms.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Extensively drug-resistant (XDR) Pseudomonas aeruginosa ST463 strains present significant clinical challenges due to co-harbored metallo-beta-lactamase (MBL) and blaKPC-2 genes.
  • These strains exhibit high levels of resistance and virulence, complicating treatment options.

Purpose of the Study:

  • To characterize the plasmids and mobile genetic elements associated with XDR P. aeruginosa ST463.
  • To elucidate the genetic mechanisms underlying the acquisition and evolution of antimicrobial resistance genes in these strains.

Main Methods:

  • Whole-genome sequencing and plasmid analysis of three XDR P. aeruginosa ST463 isolates (PA64, PA3117, PA30).
  • Identification and characterization of plasmid types, including IncP-2 megaplasmids and type I plasmids.
  • Analysis of transposons, integrons, and insertion sequences associated with antimicrobial resistance genes.

Main Results:

  • All three strains harbored a ~450 kb IncP-2 megaplasmid and a type I plasmid carrying the blaKPC-2 gene.
  • The IncP-2 megaplasmids were associated with variable Tn1403-like transposons (Tn6485g, Tn6485h, Tn6485f).
  • Tn6485g carried blaIMP-45 within the In786 integron, followed by ISCR1-armA and Tn6309. Tn6485h acquired additional ISCR1-associated modules, resulting in two MBL genes (blaIMP-45 and blaAFM-1). Tn6485f contained an additional ISCR1-qnrVC6 copy.

Conclusions:

  • The IncP-2 megaplasmids serve as a platform for the acquisition and dissemination of diverse antimicrobial resistance genes.
  • The evolution of Tn1403-like transposons, driven by ISCR1-associated modules under antibiotic pressure, contributes to the emergence of multidrug resistance in P. aeruginosa.
  • Understanding these genetic mechanisms is crucial for developing effective strategies against XDR bacterial infections.
Keywords:
IncP-2 megaplasmidKPC-2Pseudomonas aeruginosaST463Tn1403-like transposon

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