Identification of a Novel Clone, ST736, among Enterococcus faecium Clinical Isolates and Its Association with Daptomycin Nonsusceptibility

Abstract

Resistance to daptomycin in enterococcal clinical isolates remains rare but is being increasingly reported in the United States and worldwide. There are limited data on the genetic relatedness and microbiological and clinical characteristics of daptomycinnonsusceptible enterococcal clinical isolates. In this study, we assessed the population genetics of daptomycin-nonsusceptible Enterococcus faecium (DNSE) clinical isolates by multilocus sequence typing (MLST) and whole-genome sequencing analysis. Forty-two nonduplicate DNSE isolates and 43 randomly selected daptomycin-susceptible E. faecium isolates were included in the analysis. All E. faecium isolates were recovered from patients at a tertiary care medical center in suburban New York City from May 2009 through December 2013. The daptomycin MICs of the DNSE isolates ranged from 6 to >256 g/ml. Three major clones of E. faecium (ST18, ST412, and ST736) were identified among these clinical isolates by MLST and whole-genome sequence-based analysis. A newly recognized clone, ST736, was seen in 32 of 42 (76.2%) DNSE isolates and in only 14 of 43 (32.6%) daptomycin-susceptible E. faecium isolates (P < 0.0001). This report provides evidence of the association between E. faecium clone ST736 and daptomycin nonsusceptibility. The identification and potential spread of this novel E. faecium clone and its association with daptomycin nonsusceptibility constitute a challenge for patient management and infection control at our medical center.

Genetic Basis of Emerging Vancomycin, Linezolid, and Daptomycin Heteroresistance in a Case of Persistent Enterococcus faecium Bacteremia

“…Multilocus sequence typing indicated that all strains were sequence type 736 (ST736). This clone is associated with reduced susceptibility and nonsusceptibility to daptomycin (MIC = 3 to 4 μg/ml) due to the presence of liaS Thr120→Ala and liaR Trp73→Cys substitutions ( 17 ). The same substitutions were identified in all sequenced strains ( Fig.…”

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

“…Recently, we identified a novel clone ST736 that accounts for 76.6% of daptomycin-nonsusceptible E . faecium isolates at our institution [27]. Since then, ST736 strains have been expanding to other hospitals in New York [28, 29], Washington [29, 30], Texas [15, 31], Maryland (https://pubmlst.org/efaecium/), Canada [32], countries in South America [15] and Caribbean [33], as well as Germany [34].…”

Structural Basis for Enhancement of Carbapenemase Activity in the OXA-51 Family of Class D β-Lactamases

“…The overall structure of OXA-51 resembles that of other class D β-lactamases whose structures have been determined, including OXA-1, 26,27 OXA-2 (unpublished, PDB code 1K38), OXA-10, 28,29 OXA-13, 30 OXA-23, 25,31 OXA-24, 32,33 OXA-45 (unpublished, PDB code 4GN2), OXA-46, 34 OXA-48, 35 OXA-58, 36 and OXA-146. 31 Superposition of OXA-51 onto these enzymes gives rmsds for all matching C α atoms ranging from 0.6 Å for OXA-23 and OXA-24 up to 1.8 Å for OXA-45 (Table S1). Not surprisingly, OXA-51 shows high structural agreement with the four other OXA enzymes from A. baumannii (OXA-23, -24, -58 and -143), consistent with a significant degree of sequence identity (54% to 67%) between these five enzymes.…”