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Rapid in vivo development of resistance to daptomycin in vancomycin-resistant Enterococcus faecium due to genomic alterations

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Daptomycin 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 analyzed the genomic changes leading to a daptomycin-susceptible VREfm isolate becoming resistant after 50 days of daptomycin and linezolid combination therapy. A total of seven isogenic VREfm isolates from the same patient (daptomycin-susceptible and daptomycin-resistant) were analyzed using Illumina whole genome sequencing, and two isolates were further characterized with Nanopore sequencing. One nonsynonymous SNP in the rpoC gene previously shown to harbor mutations in daptomycin-resistant VREfm was identified in the daptomycin-resistant isolates. Whole genome comparative analysis identified the loss of a 46.5 kb fragment, duplication of a 29.7 kb fragment, and integration of two plasmids upon acquisition of daptomycin resistance. Transmission electron microscopy showed similar alterations in cell morphology and cell wall structure as have previously been described in daptomycin-resistant E. faecalis.

Original languageEnglish
Article numberfnac063
JournalFEMS Microbiology Letters
Issue number1
Publication statusPublished - 13 Aug 2022

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.

    Research areas

  • Anti-Bacterial Agents/pharmacology, Cross Infection, Daptomycin/pharmacology, Enterococcus faecium/genetics, Genomics, Gram-Positive Bacterial Infections/drug therapy, Humans, Microbial Sensitivity Tests, Vancomycin-Resistant Enterococci/genetics, Vancomycin/pharmacology, mannose pathway, cell envelope, rpoC, VRE, Enterococcus faecium, vancomycin resistance, daptomycin resistance

ID: 79863954