Plasmid-mediated metronidazole resistance in Clostridioides difficile

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.