Plasmid-mediated metronidazole resistance in Clostridioides difficile

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 and Wiep Klaas Smits ()
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Ilse M. Boekhoud: Leiden University Medical Center
Bastian V. H. Hornung: 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
Wiep Klaas Smits: Leiden University Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14382-1

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