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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

CTX-M-type extended-spectrum beta-lactamase that hydrolyzes ceftazidime through a single amino acid substitution in

L Poirel1, T Naas, I Le Thomas

  • 1Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre Cedex, France.

Antimicrobial Agents and Chemotherapy
|November 16, 2001
PubMed

Insights

Two novel beta-lactamase enzymes, CTX-M-18 and CTX-M-19, were identified in Escherichia coli and Klebsiella pneumoniae isolates. These enzymes confer resistance to expanded-spectrum cephalosporins, with CTX-M-19 showing unique ceftazidime hydrolysis.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Extended-spectrum cephalosporins are crucial antibiotics for treating Gram-negative bacterial infections.
  • The emergence of beta-lactamase enzymes poses a significant threat to the efficacy of these life-saving drugs.
  • CTX-M-type beta-lactamases are a growing concern due to their prevalence and ability to hydrolyze a broad range of beta-lactam antibiotics.

Purpose of the Study:

  • To characterize novel beta-lactamase enzymes identified in clinical isolates of Escherichia coli and Klebsiella pneumoniae.
  • To elucidate the genetic basis and biochemical properties of these newly discovered enzymes.
  • To investigate the potential for horizontal gene transfer of the genes encoding these beta-lactamases.

Main Methods:

  • Bacterial isolation and identification from clinical samples.
  • Antimicrobial susceptibility testing, including determination of minimum inhibitory concentrations (MICs).
  • Genetic analysis (gene sequencing) and biochemical characterization of beta-lactamase enzymes.
  • Plasmid analysis to assess the location and transferability of resistance genes.

Main Results:

  • Isolation of three bacterial strains: Escherichia coli ILT-1, Klebsiella pneumoniae ILT-2, and K. pneumoniae ILT-3.
  • Identification of CTX-M-18 beta-lactamase in E. coli ILT-1 and K. pneumoniae ILT-2.
  • Identification of CTX-M-19 beta-lactamase in K. pneumoniae ILT-3.
  • Differential resistance profiles observed for cefotaxime and ceftazidime.
  • Amino acid substitutions in CTX-M-19 (Pro167Ser) potentially responsible for ceftazidime hydrolysis.
  • bla(CTX-M-18) and bla(CTX-M-19) genes found on transferable plasmids of approximately 60 kb and 50 kb, respectively.

Conclusions:

  • Discovery of two new CTX-M beta-lactamase variants, CTX-M-18 and CTX-M-19.
  • CTX-M-19 exhibits a unique hydrolysis profile including ceftazidime, expanding the known substrate range for CTX-M enzymes.
  • The presence of these genes on transferable plasmids highlights the potential for rapid dissemination of cephalosporin resistance.
  • These findings underscore the importance of ongoing surveillance for novel beta-lactamases to inform antimicrobial stewardship and treatment strategies.

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