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bioRxiv · 10.1101/2021.05.07.442932

Genomic surveillance of vancomycin-resistant Enterococcus faecium reveals spread of a linear plasmid conferring a nutrient utilization advantage

Boumasmoud, M.·Dengler Haunreiter, V.·Schweizer, T. A.·Meyer, L.·Chakrakodi, B.·Schreiber, P. W.·Seidl, K.·Kühnert, D.·Kouyos, R. D.·Zinkernagel, A. S.
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Abstract

Healthcare-associated outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are a worldwide problem with increasing prevalence. The genomic plasticity of this hospital-adapted pathogen contributes to its efficient spread despite infection control measures. Here, we aimed to identify the genomic and phenotypic determinants of healthcare-associated transmission of VREfm. We assessed the VREfm transmission networks at the tertiary-care University Hospital of Zurich (USZ) between October 2014 and February 2018 and investigated microevolutionary dynamics of this pathogen. We performed whole-genome sequencing for the 69 VREfm isolates collected during this timeframe and assessed the population structure and variability of the vancomycin resistance transposon. Phylogenomic analysis allowed us to reconstruct transmission networks and to unveil external or indirect transmission networks, not detectable by traditional surveillance. Notably, it unveiled a persistent clone, sampled 31 times over a 29-month period. Exploring the evolutionary dynamics of this clone and characterizing the phenotypic consequences revealed the spread of a variant with decreased daptomycin susceptibility and the acquired ability to utilize N-acetyl-galactosamine (GalNAc), one of the primary constituents of the human gut mucins. This nutrient utilization advantage was conferred by a novel plasmid, termed pELF_USZ, which exhibited a linear topology. This plasmid, which was harbored by two distinct clones, was transferable by conjugation. Overall, this work provides an example of the potential of the integration of epidemiological, functional genomic and evolutionary perspectives to understand adaptation strategies contributing to the successful spread of VREfm. Significance statementSequencing microbial pathogens causing outbreaks has become a common practice to characterize transmission networks. In addition to the signal provided by vertical evolution, bacterial genomes harbor mobile genetic elements, shared horizontally between clones. While macroevolutionary studies have revealed an important role of plasmids and genes encoding carbohydrate utilization systems in the adaptation of Enterococcus faecium to the hospital environment, mechanisms of dissemination and the specific function of many of these genetic determinants remain to be elucidated. Here, we characterize a plasmid providing a nutrient utilization advantage and show evidence for its clonal and horizontal spread at a local scale. Further studies integrating epidemiological, functional genomics and evolutionary perspectives will be critical to identify changes shaping the success of this pathogen.

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Boumasmoud, M., Dengler Haunreiter, V., Schweizer, T. A., Meyer, L., Chakrakodi, B., Schreiber, P. W., Seidl, K., Kühnert, D., Kouyos, R. D., Zinkernagel, A. S.. 2021-05-08. Genomic surveillance of vancomycin-resistant Enterococcus faecium reveals spread of a linear plasmid conferring a nutrient utilization advantage. https://doi.org/10.1101/2021.05.07.442932

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