Haem is crucial for medium-dependent metronidazole resistance in clinical isolates of Clostridioides difficile

Boekhoud, I.M.; Sidorov, I.; Nooij, S.; Harmanus, C.; Bos-Sanders, I.M.J.G.; Viprey, V.; Spittal, W.; Clark, E.; Davies, K.; Freeman, J.; Kuijper, E.J.; Smits, W.K.; COMBACTE-CDI Consortium

doi:doi:10.1093/jac/dkab097

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...Show moreBackground: 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.Show less

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Haem is crucial for medium-dependent metronidazole resistance in clinical isolates of Clostridioides difficile