Rapid in vivo development of resistance to daptomycin in vancomycin-resistant Enterococcus faecium due to genomic alterations
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Genomic alterations and altered cell wall structure in daptomycin-resistant Enterococcus faecium revealed by comparison of isolates before and after exposure to daptomycin.
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 language | English |
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Article number | 063 |
Journal | FEMS Microbiology Letters |
Volume | 369 |
Issue number | 1 |
Number of pages | 6 |
ISSN | 0378-1097 |
DOIs | |
Publication status | Published - 2022 |
- vancomycin resistance, Enterococcus faecium, VRE, daptomycin resistance, rpoC, mannose pathway, cell envelope, READ ALIGNMENT, SUSCEPTIBILITY, MECHANISMS
Research areas
ID: 319407784