ArticleThe Journal of antimicrobial chemotherapy2018
Characterization of the impact of rpoB mutations on the in vitro and in vivo competitive fitness of Clostridium difficile and susceptibility to fidaxomicin.
Article in The Journal of antimicrobial chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Fidaxomicin resistance inAntimicrobial agents and chemotherapy · 2024Pooled it
- Clinical failure of an extended-pulsed fidaxomicin regimen associated with emergence of aAntimicrobial agents and chemotherapy · 2026Article
- Methicillin-resistantAntimicrobial agents and chemotherapy · 2026Article
- Clostridioides difficile evolution in a tertiary German hospital through a retrospective genomic characterization.Infection · 2025Article
- Emergence and Spread of Clostridioides difficile Isolates With Reduced Fidaxomicin Susceptibility in an Acute Care Hospital.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Review
- Review
- Genetic determinants of resistance to antimicrobial therapeutics are rare in publicly available Clostridioides difficile genome sequences.The Journal of antimicrobial chemotherapy · 2024Article
- Whole-genome comparison using complete genomes fromFrontiers in microbiology · 2024Article
- Antibiotic Resistances of Clostridioides difficile.Advances in experimental medicine and biology · 2024Article
- Insights into the Evolving Epidemiology ofAntibiotics (Basel, Switzerland) · 2023Review
- Antibiotic Resistance in Selected Emerging Bacterial Foodborne Pathogens-An Issue of Concern?Antibiotics (Basel, Switzerland) · 2023Review
- Mutations inmBio · 2023Article
- The absence of surface D-alanylation, localized on lipoteichoic acid, impacts theFrontiers in microbiology · 2023Article
- Fidaxomicin for the Treatment ofAntibiotics (Basel, Switzerland) · 2022Review
- Mechanisms and impact of antimicrobial resistance in Clostridioides difficile.Current opinion in microbiology · 2022Review
- Article
- Antimicrobial resistance in Clostridioides difficile.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021Review
- Mechanisms of antibiotic resistance of Clostridioides difficile.The Journal of antimicrobial chemotherapy · 2021Review
- Antimicrobial resistance in enteric bacteria: current state and next-generation solutions.Gut microbes · 2020Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Objectives: To establish the role of specific, non-synonymous SNPs in the RNA polymerase β subunit (rpoB) gene in reducing the susceptibility of Clostridium difficile to fidaxomicin and to explore the potential in vivo significance of rpoB mutant strains. Methods: Allelic exchange was used to introduce three different SNPs into the rpoB gene of an erythromycin-resistant derivative (CRG20291) of C. difficile R20291. The genome sequences of the created mutants were determined and each mutant analysed with respect to growth and sporulation rates, toxin A/B production and cytotoxicity against Vero cells, and in competition assays. Their comparative virulence and colonization ability was also assessed in a hamster infection model. Results: The MIC of fidaxomicin displayed by three mutants CRG20291-TA, CRG20291-TG and CRG20291-GT was substantially increased (>32, 8 and 2 mg/L, respectively) relative to that of the parent strain (0.25 mg/L). Genome sequencing established that the intended mutagenic substitutions in rpoB were the only changes present. Relative to CRG20291, all mutants had attenuated growth, were outcompeted by the parental strain, had lower sporulation and toxin A/B production capacities, and displayed diminished cytotoxicity. In a hamster model, virulence of all three mutants was significantly reduced compared with the progenitor strain, whereas the degree of caecum colonization was unaltered. Conclusions: Our study demonstrates that particular SNPs in rpoB lead to reduced fidaxomicin susceptibility. These mutations were associated with a fitness cost in vitro and reduced virulence in vivo.
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