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Characterization of a clinical Clostridioides difficile isolate with markedly reduced fidaxomicin susceptibility and a V1143D mutation in rpoB.
- Source :
-
Journal of Antimicrobial Chemotherapy (JAC) . Jan2019, Vol. 74 Issue 1, p6-10. 5p. - Publication Year :
- 2019
-
Abstract
- <bold>Objectives: </bold>The identification and characterization of clinical Clostridioides difficile isolates with reduced fidaxomicin susceptibility.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CLOSTRIDIOIDES difficile
*MICROBIAL virulence
*DRUG resistance in bacteria
*NUCLEOTIDE sequencing
*FIDAXOMICIN
*ANTIBIOTICS
*CLOSTRIDIUM diseases
*COMPARATIVE studies
*RESEARCH methodology
*MEDICAL cooperation
*MICROBIAL sensitivity tests
*GENETIC mutation
*POLYMERASE chain reaction
*RESEARCH
*TRANSFERASES
*EVALUATION research
*SEQUENCE analysis
*PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 03057453
- Volume :
- 74
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Antimicrobial Chemotherapy (JAC)
- Publication Type :
- Academic Journal
- Accession number :
- 133582937
- Full Text :
- https://doi.org/10.1093/jac/dky375