Characterization of a clinical Clostridioides difficile isolate with markedly reduced fidaxomicin susceptibility and a V1143D mutation in rpoB
| العنوان: | Characterization of a clinical Clostridioides difficile isolate with markedly reduced fidaxomicin susceptibility and a V1143D mutation in rpoB |
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| المؤلفون: | Wolfgang Bohne, Ines Oehmig, Andreas E. Zautner, Isabel Schober, Ortrud Zimmermann, Julian Schwanbeck, Thomas Riedel, Friederike Laukien, Jörg Overmann, Uwe Groß |
| المصدر: | Journal of Antimicrobial Chemotherapy. 74:6-10 |
| بيانات النشر: | Oxford University Press (OUP), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Microbiology (medical), 030106 microbiology, Mutant, Mutation, Missense, Clostridium difficile toxin A, Microbial Sensitivity Tests, Biology, medicine.disease_cause, Polymerase Chain Reaction, Agar dilution, Microbiology, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, medicine, Humans, Missense mutation, Pharmacology (medical), Fidaxomicin, 030212 general & internal medicine, Polymerase chain reaction, Pharmacology, Clostridioides difficile, Toxin, DNA-Directed RNA Polymerases, Sequence Analysis, DNA, rpoB, Anti-Bacterial Agents, Infectious Diseases, Clostridium Infections, medicine.drug |
| الوصف: | Objectives The identification and characterization of clinical Clostridioides difficile isolates with reduced fidaxomicin susceptibility. Methods Agar dilution assays were used to determine fidaxomicin MICs. Genome sequence data were obtained by single-molecule real-time (SMRT) sequencing in addition to amplicon sequencing of rpoB and rpoC alleles. Allelic exchange was used to introduce the identified mutation into C. difficile 630Δerm. Replication rates, toxin A/B production and spore formation were determined from the strain with reduced fidaxomicin susceptibility. Results Out of 50 clinical C. difficile isolates, isolate Goe-91 revealed markedly reduced fidaxomicin susceptibility (MIC >64 mg/L). A V1143D mutation was identified in rpoB of Goe-91. When introduced into C. difficile 630Δerm, this mutation decreased fidaxomicin susceptibility (MIC >64 mg/L), but was also associated with a reduced replication rate, low toxin A/B production and markedly reduced spore formation. In contrast, Goe-91, although also reduced in toxin production, showed normal growth rates and only moderately reduced spore formation capacities. This indicates that the rpoBV1143D allele-associated fitness defect is less pronounced in the clinical isolate. Conclusions To the best of our knowledge, this is the first description of a pathogenic clinical C. difficile isolate with markedly reduced fidaxomicin susceptibility. The lower-than-expected fitness burden of the resistance-mediating rpoBV1143D allele might be an indication for compensatory mechanisms that take place during in vivo selection of mutants. |
| تدمد: | 1460-2091 0305-7453 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4e4fa170a72d1d1677ef491aabfcc23fTest https://doi.org/10.1093/jac/dky375Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4e4fa170a72d1d1677ef491aabfcc23f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602091 03057453 |
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