Rapid in vivo development of resistance to daptomycin in vancomycin-resistant Enterococcus faecium due to genomic alterations
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Rapid in vivo development of resistance to daptomycin in vancomycin-resistant Enterococcus faecium due to genomic alterations. / Mollerup, Sarah; Elmeskov, Christine; Pinholt, Mette; Sejersen, Tobias S.; Pedersen, Martin S.; Worning, Peder; Frees, Dorte; Westh, Henrik.
I: FEMS Microbiology Letters, Bind 369, Nr. 1, 063, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Rapid in vivo development of resistance to daptomycin in vancomycin-resistant Enterococcus faecium due to genomic alterations
AU - Mollerup, Sarah
AU - Elmeskov, Christine
AU - Pinholt, Mette
AU - Sejersen, Tobias S.
AU - Pedersen, Martin S.
AU - Worning, Peder
AU - Frees, Dorte
AU - Westh, Henrik
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - vancomycin resistance
KW - Enterococcus faecium
KW - VRE
KW - daptomycin resistance
KW - rpoC
KW - mannose pathway
KW - cell envelope
KW - READ ALIGNMENT
KW - SUSCEPTIBILITY
KW - MECHANISMS
U2 - 10.1093/femsle/fnac063
DO - 10.1093/femsle/fnac063
M3 - Journal article
C2 - 35922088
VL - 369
JO - F E M S Microbiology Letters
JF - F E M S Microbiology Letters
SN - 0378-1097
IS - 1
M1 - 063
ER -
ID: 319407784