1. Haem is crucial for medium-dependent metronidazole resistance in clinical isolates of Clostridioides difficile.
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Boekhoud, Ilse M, Sidorov, Igor, Nooij, Sam, Harmanus, Céline, Bos-Sanders, Ingrid M J G, Viprey, Virginie, Spittal, William, Clark, Emma, Davies, Kerrie, Freeman, Jane, Kuijper, Ed J, Smits, Wiep Klaas, Consortium, the COMBACTE-CDI, and COMBACTE-CDI Consortium
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CLOSTRIDIOIDES difficile ,HEME ,METRONIDAZOLE ,MICROBIAL sensitivity tests - Abstract
Background: Until recently, metronidazole was the first-line treatment for Clostridioides difficile infection and it is still commonly used. Though resistance has been reported due to the plasmid pCD-METRO, this does not explain all cases.Objectives: To identify factors that contribute to plasmid-independent metronidazole resistance of C. difficile.Methods: Here, we investigate resistance to metronidazole in a collection of clinical isolates of C. difficile using a combination of antimicrobial susceptibility testing on different solid agar media and WGS of selected isolates.Results: We find that nearly all isolates demonstrate a haem-dependent increase in the MIC of metronidazole, which in some cases leads to isolates qualifying as resistant (MIC >2 mg/L). Moreover, we find an SNP in the haem-responsive gene hsmA, which defines a metronidazole-resistant lineage of PCR ribotype 010/MLST ST15 isolates that also includes pCD-METRO-containing strains.Conclusions: Our data demonstrate that haem is crucial for medium-dependent metronidazole resistance in C. difficile. [ABSTRACT FROM AUTHOR]- Published
- 2021
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