Rapid in vivo development of resistance to daptomycin in vancomycin-resistant Enterococcus faecium due to genomic rearrangements
| Autor: | Tobias Steen Sejersen, Christine Elmeskov, Sarah Mollerup, Martin Schou Pedersen, Mette Pinholt, Peder Worning, Dorte Frees, Henrik Westh, Heidi Gumpert |
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| Rok vydání: | 2021 |
| Předmět: |
Genetics
Whole genome sequencing biochemical phenomena metabolism and nutrition Biology bacterial infections and mycoses biology.organism_classification Genome chemistry.chemical_compound Plasmid chemistry Gene duplication Linezolid polycyclic compounds medicine lipids (amino acids peptides and proteins) Daptomycin Gene Enterococcus faecium medicine.drug |
| Popis: | BackgroundDaptomycin is a cyclic lipopeptide used in the treatment of vancomycin-resistant Enterococcus faecium (VREfm). However, the development of daptomycin-resistant VREfm challenges the treatment of nosocomial VREfm infections. Resistance mechanisms of daptomycin are not fully understood. Here we analysed the genomic changes leading to a daptomycin-susceptible VREfm isolate becoming resistant after 40 days of daptomycin and linezolid combination therapy.MethodsThe two isogenic VREfm isolates (daptomycin-susceptible and daptomycin-resistant) were analysed using whole genome sequencing with Illumina and Nanopore.ResultsWhole genome comparative analysis identified the loss of a 46.5 kb fragment and duplication of a 29.7 kb fragment in the daptomycin-resistant isolate, with many implicated genes involved in cell wall synthesis. Two plasmids of the daptomycin-susceptible isolate were also found integrated in the chromosome of the resistant isolate. One nonsynonymous SNP in the rpoC gene was identified in the daptomycin-resistant isolate.ConclusionsDaptomycin resistance developed through chromosomal rearrangements leading to altered cell wall structure. Such novel types of resistance mechanisms can only be identified by comparing closed genomes of isogenic isolates. |
| Databáze: | OpenAIRE |
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