1. Heme is crucial for medium-dependent metronidazole resistance in clinical isolates of C. difficile
- Author
-
E.J. Kuijper, Igor A. Sidorov, Ingrid M. J. G. Bos-Sanders, Spittal B, Ilse M. Boekhoud, Viprey, Kerrie Davies, Emma Clark, Wiep Klaas Smits, Celine Harmanus, Jane Freeman, and Sam Nooij
- Subjects
Lineage (genetic) ,Single-nucleotide polymorphism ,Biology ,Microbiology ,Minimum inhibitory concentration ,chemistry.chemical_compound ,Metronidazole ,Plasmid ,chemistry ,medicine ,Heme ,Gene ,Metronidazole resistance ,medicine.drug - Abstract
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. Here, we investigate resistance to metronidazole in a collection of clinical isolates of C. difficile. We find that nearly all isolates demonstrate a heme-dependent increase in the minimal inhibitory concentration for metronidazole, which in some cases leads to isolates being qualified as resistant (MIC > 2 mg/L). Moreover, whole genome sequence analysis reveals a single nucleotide polymorphism in the heme responsive gene hsmA, which defines a metronidazole resistant lineage of PCR ribotype 010 / multilocus sequence type 15 isolates that also includes pCD-METRO containing strains. Together our data demonstrate that heme is crucial for medium-dependent metronidazole resistance in C. difficile.
- Published
- 2020