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PLoS One. 2018 Dec 21;13(12):e0209785. doi: 10.1371/journal.pone.0209785. eCollection 2018.

Evolution and mutations predisposing to daptomycin resistance in vancomycin-resistant Enterococcus faecium ST736 strains.

Author information

1
Department of Pathology, New York Medical College, Valhalla, New York, United States of America.
2
Department of Pathology and Clinical Laboratories, Westchester Medical Center, Valhalla, Valhalla, New York, United States of America.
3
Philips Research North America, Cambridge, Massachusetts, United States of America.
4
Department of Medicine, New York Medical College, Valhalla, New York, United States of America.
5
Department of Pharmacy, Westchester Medical Center, Valhalla, New York, United States of America.

Abstract

We recently identified a novel vancomycin-resistant Enterococcus faecium (VREfm) clone ST736 with reduced daptomycin susceptibility. The objectives of this study were to assess the population dynamics of local VREfm strains and genetic alterations predisposing to daptomycin resistance in VREfm ST736 strains. Multilocus sequence typing and single nucleotide variant data were derived from whole-genome sequencing of 250 E. faecium isolates from 1994-1995 (n = 43), 2009-2012 (n = 115) and 2013 (n = 92). A remarkable change was noticed in the clonality and antimicrobial resistance profiles of E. faecium strains between 1994-1995 and 2013. VREfm sequence type 17 (ST17), the prototype strain of clade A1, was the dominant clone (76.7%) recognized in 1994-1995. By contrast, clone ST736 accounted for 46.7% of VREfm isolates, followed by ST18 (26.1%) and ST412 (20.7%) in 2013. Bayesian evolutionary analysis suggested that clone ST736 emerged between 1996 and 2009. Co-mutations (liaR.W73C and liaS.T120A) of the liaFSR system were identified in all ST736 isolates (n = 111, 100%) examined. Thirty-eight (34.2%) ST736 isolates exhibited daptomycin-resistant phenotype, of which 13 isolates had mutations in both the liaFSR and cardiolipin synthase (cls) genes and showed high level of resistance with a daptomycin MIC50 of 32 μg/mL. The emergence of ST736 strains with mutations predisposing to daptomycin resistance and subsequent clonal spread among inpatients contributed to the observed high occurrence of daptomycin resistance in VREfm at our institution. The expanding geographic distribution of ST736 strains in other states and countries raises concerns about its global dissemination.

Conflict of interest statement

G.W has received grant support from Cubist Pharmaceuticals. A.D. is on the speaker’s bureau of and has received honoraria from Cubist Pharmaceuticals. J.T. F. has received research funding from the Philips Healthcare. All other authors: none to declare. We confirm that the commercial affiliation of authors does not alter our adherence to PLOS ONE policies on sharing data and materials.

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