Abstract
BackgroundEnterococcus faecium is a commensal of the gastrointestinal tract of animals and humans but also a causative agent of hospital-acquired infections. Resistance against glycopeptides and to vancomycin has motivated the inclusion of E. faecium in the WHO global priority list. Vancomycin resistance can be conferred by the vanA gene cluster on the transposon Tn1546, which is frequently present in plasmids. The vanA gene cluster can be disseminated clonally but also horizontally either by plasmid dissemination or by Tn1546 transposition between different genomic locations.MethodsWe performed a retrospective study of the genomic epidemiology of 309 vancomycin-resistant E. faecium (VRE) isolates across 32 Dutch hospitals (2012–2015). Genomic information regarding clonality and Tn1546 characterization was extracted using hierBAPS sequence clusters (SC) and TETyper, respectively. Plasmids were predicted using gplas in combination with a network approach based on shared k-mer content. Next, we conducted a pairwise comparison between isolates sharing a potential epidemiological link to elucidate whether clonal, plasmid, or Tn1546 spread accounted for vanA-type resistance dissemination.ResultsOn average, we estimated that 59% of VRE cases with a potential epidemiological link were unrelated which was defined as VRE pairs with a distinct Tn1546 variant. Clonal dissemination accounted for 32% cases in which the same SC and Tn1546 variants were identified. Horizontal plasmid dissemination accounted for 7% of VRE cases, in which we observed VRE pairs belonging to a distinct SC but carrying an identical plasmid and Tn1546 variant. In 2% of cases, we observed the same Tn1546 variant in distinct SC and plasmid types which could be explained by mixed and consecutive events of clonal and plasmid dissemination.ConclusionsIn related VRE cases, the dissemination of the vanA gene cluster in Dutch hospitals between 2012 and 2015 was dominated by clonal spread. However, we also identified outbreak settings with high frequencies of plasmid dissemination in which the spread of resistance was mainly driven by horizontal gene transfer (HGT). This study demonstrates the feasibility of distinguishing between modes of dissemination with short-read data and provides a novel assessment to estimate the relative contribution of nested genomic elements in the dissemination of vanA-type resistance.
Highlights
Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans and a causative agent of hospital-acquired infections
The population structure of vancomycin-resistant Enterococcus faecium (VRE) from Dutch hospitals This study was conducted with samples from an extensive collection of 1644 E. faecium isolates derived from clinical and non-clinical sources with associated short-read whole-genome sequencing (WGS) data [21]
In Additional File 3, we provide a detailed genomic characterization of the plasmid types (A–I) with a focus on (i) replication initiator proteins, (ii) Tn1546 variant compared to the original sequence described by Arthur et al [32], (iii) antimicrobial resistance (AMR) genes distinct from the vanA gene cluster, and (iv) presence of well-known E. faecium plasmid toxin-antitoxin systems such as ω-ε-ζ and axe-txe [47]
Summary
Enterococcus faecium is a commensal of the gastrointestinal tract of animals and humans and a causative agent of hospital-acquired infections. Clonal spread of vancomycin-resistant Enterococcus faecium (VRE) has been extensively described using a plethora of molecular typing schemes They range from fingerprint-based methods like pulsed-field gel electrophoresis [8] to PCR-based methods such as multiplelocus variable number tandem repeat analysis [9], multilocus sequence typing [10], and whole-genome sequencing [11]. To identify the dissemination of vanA plasmids within hospital settings, whole-genome sequencing (WGS) based on short-read technologies has been recently applied to collections of hundred hospitalized patient isolates in Denmark and Australia [14, 15] These studies undertook a referencebased approach to map short-reads against complete plasmids from a selection of isolates. This approach can overestimate the presence of a reference plasmid by neglecting the mosaicism observed in these types of sequences as previously observed for Enterobacteriaceae isolates [16] and Enterococcus populations [17]
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