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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

Plasmid-encoded metallo-beta-lactamase (IMP-6) conferring resistance to carbapenems, especially meropenem

H Yano1, A Kuga, R Okamoto

  • 1Department of Microbiology, School of Medicine and Environmental Infectious Disease, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa 228-8555, Japan. d300042c@stcc.nagasaki-u.ac.jp

Antimicrobial Agents and Chemotherapy
|April 17, 2001
PubMed

Insights

A novel metallo-beta-lactamase, IMP-6, was identified in Serratia marcescens, exhibiting increased resistance to carbapenems like meropenem. This discovery offers insights into antimicrobial resistance mechanisms and potential therapeutic strategies.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Serratia marcescens is a bacterium that can cause infections, including urinary tract infections.
  • Plasmids, such as pKU501, can carry genes conferring antibiotic resistance.
  • Metallo-beta-lactamases are enzymes that can inactivate beta-lactam antibiotics, including carbapenems.

Purpose of the Study:

  • To characterize a novel metallo-beta-lactamase, designated IMP-6, identified in Serratia marcescens.
  • To investigate the substrate profile and resistance patterns conferred by IMP-6.
  • To understand the genetic basis of IMP-6 and its impact on carbapenem resistance.

Main Methods:

  • Isolation and identification of Serratia marcescens KU3838.
  • Plasmid DNA extraction and characterization (pKU501 and pKU502).
  • PCR amplification and DNA sequencing of the metallo-beta-lactamase gene.
  • Determination of enzyme kinetics (kcat/Km) against various beta-lactam antibiotics.
  • Determination of minimum inhibitory concentrations (MICs) for IMP-6 producing strains.

Main Results:

  • A novel metallo-beta-lactamase gene, differing from IMP-1 by a single point mutation, was identified and designated IMP-6.
  • Strains producing IMP-6 exhibited resistance to carbapenems, with higher MICs for panipenem and meropenem compared to imipenem.
  • IMP-6 showed a sevenfold higher catalytic efficiency (kcat/Km) against meropenem than imipenem.
  • IMP-6 displayed significantly reduced activity against penicillin G and piperacillin.
  • The presence of TEM-1-type beta-lactamase on pKU501 contributed to resistance against a broader range of antimicrobial agents.

Conclusions:

  • The point mutation in IMP-6 confers enhanced activity against carbapenems, particularly meropenem, while reducing activity against penicillins.
  • IMP-6 represents a significant development in carbapenem resistance, necessitating further surveillance and understanding.
  • The co-existence of IMP-6 and TEM-1 on the same plasmid highlights the complex mechanisms of antimicrobial resistance in bacteria.

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