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Plasmid-mediated metronidazole resistance in Clostridioides difficile

Author

Listed:
  • Ilse M. Boekhoud

    (Leiden University Medical Center
    Centre for Microbial Cell Biology
    Netherlands Centre for One Health)

  • Bastian V. H. Hornung

    (Leiden University Medical Center
    Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center)

  • Eloisa Sevilla

    (Universidad de Zaragoza)

  • Céline Harmanus

    (Leiden University Medical Center)

  • Ingrid M. J. G. Bos-Sanders

    (Leiden University Medical Center)

  • Elisabeth M. Terveer

    (Leiden University Medical Center)

  • Rosa Bolea

    (Universidad de Zaragoza)

  • Jeroen Corver

    (Leiden University Medical Center)

  • Ed J. Kuijper

    (Leiden University Medical Center
    Netherlands Centre for One Health
    Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center
    National Institute for Public Health and the Environment)

  • Wiep Klaas Smits

    (Leiden University Medical Center
    Centre for Microbial Cell Biology
    Netherlands Centre for One Health)

Abstract

Metronidazole was until recently used as a first-line treatment for potentially life-threatening Clostridioides difficile (CD) infection. Although cases of metronidazole resistance have been documented, no clear mechanism for metronidazole resistance or a role for plasmids in antimicrobial resistance has been described for CD. Here, we report genome sequences of seven susceptible and sixteen resistant CD isolates from human and animal sources, including isolates from a patient with recurrent CD infection by a PCR ribotype (RT) 020 strain, which developed resistance to metronidazole over the course of treatment (minimal inhibitory concentration [MIC] = 8 mg L−1). Metronidazole resistance correlates with the presence of a 7-kb plasmid, pCD-METRO. pCD-METRO is present in toxigenic and non-toxigenic resistant (n = 23), but not susceptible (n = 563), isolates from multiple countries. Introduction of a pCD-METRO-derived vector into a susceptible strain increases the MIC 25-fold. Our finding of plasmid-mediated resistance can impact diagnostics and treatment of CD infections.

Suggested Citation

  • Ilse M. Boekhoud & Bastian V. H. Hornung & Eloisa Sevilla & Céline Harmanus & Ingrid M. J. G. Bos-Sanders & Elisabeth M. Terveer & Rosa Bolea & Jeroen Corver & Ed J. Kuijper & Wiep Klaas Smits, 2020. "Plasmid-mediated metronidazole resistance in Clostridioides difficile," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14382-1
    DOI: 10.1038/s41467-020-14382-1
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    Cited by:

    1. Abiola O. Olaitan & Chetna Dureja & Madison A. Youngblom & Madeline A. Topf & Wan-Jou Shen & Anne J. Gonzales-Luna & Aditi Deshpande & Kirk E. Hevener & Jane Freeman & Mark H. Wilcox & Kelli L. Palmer, 2023. "Decoding a cryptic mechanism of metronidazole resistance among globally disseminated fluoroquinolone-resistant Clostridioides difficile," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Geoffroy, Félix & Uecker, Hildegard, 2023. "Limits to evolutionary rescue by conjugative plasmids," Theoretical Population Biology, Elsevier, vol. 154(C), pages 102-117.

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