1. Haem is crucial for medium-dependent metronidazole resistance in clinical isolates of Clostridioides difficile
- Author
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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, Bonten, Marc, Davies, Kerrie A, Rupnik, Maja, Wingen-Heiman, Sebastian, Tacconelli, Evelina, Wilken, Tuba, Petrosillo, Nicolla, Cleuziat, Philippe, Webber, Chris, and Wilcox, Mark
- Subjects
Microbiology (medical) ,food.ingredient ,Antimicrobial susceptibility ,Heme ,Microbial Sensitivity Tests ,Biology ,Ribotyping ,law.invention ,Microbiology ,03 medical and health sciences ,Plasmid ,food ,Clostridioides ,law ,Metronidazole ,medicine ,Agar ,AcademicSubjects/MED00740 ,Humans ,Pharmacology (medical) ,Polymerase chain reaction ,030304 developmental biology ,Metronidazole resistance ,Original Research ,Pharmacology ,0303 health sciences ,030306 microbiology ,Clostridioides difficile ,3. Good health ,Anti-Bacterial Agents ,Infectious Diseases ,AcademicSubjects/MED00290 ,Clostridium Infections ,Multilocus sequence typing ,AcademicSubjects/MED00230 ,medicine.drug ,Multilocus Sequence Typing - 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.
- Published
- 2021