Genomic confirmation of vancomycin-resistant Enterococcus transmission from deceased donor to liver transplant recipient

Bashir, Ali Kashif; Attie, Oliver; Sullivan, Mitchell J.; Sebra, Robert; Singh, Kavindra V.; Altman, Deena R.; Pak, Theodore R.; Dutta, Jayeeta; Chacko, Kieran I.; Webster, Elizabeth; Lewis, Martha; Hamula, Camille; Carpini, Kristin W. Delli; Murray, Barbara E.; Kasarskis, Andrew; Bakel, Harm van; Huprikar, Shirish

doi:10.1371/journal.pone.0170449

Cited by 17 publications

(9 citation statements)

References 35 publications

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“…In contrast to other patients, E. faecium was not recovered from stool obtained 9 and 5 days prior to the onset of bacteraemia but blood isolates clustered with stool and environmental isolates cultured subsequently (Additional file 3 : Figure S7). The van genes resided on a different plasmid to the other cases, the plasmid backbone contained a replicon recovered previously from an individual in New York, USA (plasmid accession ID CP018831) [ 36 ], our data showing 68% coverage of that plasmid. One blood isolate was vancomycin susceptible and lacked the whole plasmid, including the resistance gene (Additional file 3 : Figure S7).…”

Section: Resultsmentioning

confidence: 89%

Within-host evolution of Enterococcus faecium during longitudinal carriage and transition to bloodstream infection in immunocompromised patients

et al. 2017

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Background Enterococcus faecium is a leading cause of hospital-acquired infection, particularly in the immunocompromised. Here, we use whole genome sequencing of E. faecium to study within-host evolution and the transition from gut carriage to invasive disease.MethodsWe isolated and sequenced 180 E. faecium from four immunocompromised patients who developed bloodstream infection during longitudinal surveillance of E. faecium in stool and their immediate environment.ResultsA phylogenetic tree based on single nucleotide polymorphisms (SNPs) in the core genome of the 180 isolates demonstrated several distinct clones. This was highly concordant with the population structure inferred by Bayesian methods, which contained four main BAPS (Bayesian Analysis of Population Structure) groups. The majority of isolates from each patient resided in a single group, but all four patients also carried minority populations in stool from multiple phylogenetic groups. Bloodstream isolates from each case belonged to a single BAPS group, which differed in all four patients. Analysis of 87 isolates (56 from blood) belonging to a single BAPS group that were cultured from the same patient over 54 days identified 30 SNPs in the core genome (nine intergenic, 13 non-synonymous, eight synonymous), and 250 accessory genes that were variably present. Comparison of these genetic variants in blood isolates versus those from stool or environment did not identify any variants associated with bloodstream infection. The substitution rate for these isolates was estimated to be 128 (95% confidence interval 79.82 181.77) mutations per genome per year, more than ten times higher than previous estimates for E. faecium. Within-patient variation in vancomycin resistance associated with vanA was common and could be explained by plasmid loss, or less often by transposon loss.ConclusionsThese findings demonstrate the diversity of E. faecium carriage by individual patients and significant within-host diversity of E. faecium, but do not provide evidence for adaptive genetic variation associated with invasion.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-017-0507-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 89%

Within-host evolution of Enterococcus faecium during longitudinal carriage and transition to bloodstream infection in immunocompromised patients

et al. 2017

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“…Although we did not detect heteroresistance in the original A isolate, it is likely that low-level resistance was already present below the detectable limit. We consider horizontal gene transfer less plausible, especially considering that older ST736 isolates collected at Mount Sinai Hospital ( 37 ) all contained nearly identical 41-kb vanA resistance plasmids.…”

Section: Textmentioning

confidence: 99%

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

Chacko

Sullivan

Beckford

et al. 2018

Antimicrob Agents Chemother

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Whole-genome sequencing was used to examine a persistent Enterococcus faecium bacteremia that acquired heteroresistance to three antibiotics in response to prolonged multidrug therapy. A comparison of the complete genomes before and after each change revealed the emergence of known resistance determinants for vancomycin and linezolid and suggested that a novel mutation in fabF, encoding a fatty acid synthase, was responsible for daptomycin nonsusceptibility. Plasmid recombination contributed to the progressive loss of vancomycin resistance after withdrawal of the drug.

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“…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]. Moreover and the most worrisome, ST736 has been reported as the most common VREfm strains on hospital environmental surfaces and in laundry facility of some US teaching hospitals [31, 35].…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Lin

et al. 2018

PLoS ONE

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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.

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Genomic confirmation of vancomycin-resistant Enterococcus transmission from deceased donor to liver transplant recipient

Cited by 17 publications

References 35 publications

Within-host evolution of Enterococcus faecium during longitudinal carriage and transition to bloodstream infection in immunocompromised patients

Within-host evolution of Enterococcus faecium during longitudinal carriage and transition to bloodstream infection in immunocompromised patients

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

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

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