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Plasmid-mediated metronidazole resistance in Clostridioides difficile

Ilse M Boekhoud1,2,3, Bastian V H Hornung1,4, Eloisa Sevilla5

  • 1Department of Medical Microbiology, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC, Leiden, The Netherlands.

Nature Communications
|February 1, 2020
PubMed

Insights

A newly discovered plasmid, pCD-METRO, is responsible for metronidazole resistance in Clostridioides difficile (CD) infections. This finding impacts how we diagnose and treat this potentially life-threatening bacterial infection.

Area of Science:

  • Microbiology
  • Genomics
  • Antimicrobial Resistance

Background:

  • Metronidazole was a primary treatment for Clostridioides difficile (CD) infections.
  • Mechanisms of metronidazole resistance in CD were previously unclear, with no described role for plasmids.

Purpose of the Study:

  • To investigate the genetic basis of metronidazole resistance in Clostridioides difficile.
  • To identify potential mechanisms and genetic elements involved in antimicrobial resistance.

Main Methods:

  • Genome sequencing of susceptible and resistant CD isolates from human and animal sources.
  • Plasmid analysis and characterization, including the identification of pCD-METRO.
  • Introduction of plasmid-derived vectors into susceptible strains to assess resistance transfer.

Main Results:

  • Metronidazole resistance in CD isolates correlates with the presence of a 7-kb plasmid, designated pCD-METRO.
  • This plasmid was found in resistant isolates from multiple countries but absent in susceptible ones.
  • Introducing pCD-METRO into a susceptible strain significantly increased metronidazole resistance (25-fold).

Conclusions:

  • Plasmid-mediated transfer is a key mechanism for metronidazole resistance in Clostridioides difficile.
  • The identification of pCD-METRO has significant implications for the diagnostics and treatment strategies for CD infections.

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