Population structure and acquisition of the vanB resistance determinant in German clinical isolates of Enterococcus faecium ST192.

Jennifer K Bender,Carola Fleige,Ingo Klare,Stephan Fuchs,Guido Werner,Alexander Kalmbach

doi:10.1038/srep21847

Jennifer K Bender, Carola Fleige + Show 4 more

Open Access

https://doi.org/10.1038/srep21847

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Abstract

In the context of the global action plan to reduce the dissemination of antibiotic resistances it is of utmost importance to understand the population structure of resistant endemic bacterial lineages and to elucidate how bacteria acquire certain resistance determinants. Vancomycin resistant enterococci represent one such example of a prominent nosocomial pathogen on which nation-wide population analyses on prevalent lineages are scarce and data on how the bacteria acquire resistance, especially of the vanB genotype, are still under debate. With respect to Germany, an increased prevalence of VRE was noted in recent years. Here, invasive infections caused by sequence type ST192 VRE are often associated with the vanB-type resistance determinant. Hence, we analyzed 49 vanB-positive and vanB-negative E. faecium isolates by means of whole genome sequencing. Our studies revealed a distinct population structure and that spread of the Tn1549-vanB-type resistance involves exchange of large chromosomal fragments between vanB-positive and vanB-negative enterococci rather than independent acquisition events. In vitro filter-mating experiments support the hypothesis and suggest the presence of certain target sequences as a limiting factor for dissemination of the vanB element. Thus, the present study provides a better understanding of how enterococci emerge into successful multidrug-resistant nosocomial pathogens.

Highlights

IntroductionLaunay and co-workers demonstrated that Tn1549 represents a genuine transposon capable of forming a circular intermediate in order to be transferred and integrated into the target bacterial chromosome in the gut of gnotobiotic mice[10]
As vanB-positive E. faecium ST192 led to a marked increase of vancomycin-resistant enterococci (VRE) outbreaks and became a highly prevalent lineage of bloodstream infections in Germany in recent years, the present study was conducted to investigate VRE of this particular sequence type with respect to i) population structure, ii) acquisition of the vanB resistance determinant and iii) transfer of the resistance locus
As strains of ST192 have been most prevalent in recent years and have been associated with hospital-related outbreaks in German clinics[7], we set out to analyze E. faecium ST192 in more detail with respect to strain relatedness and acquisition of the composite vanB transposon Tn1549

Summary

Introduction

Launay and co-workers demonstrated that Tn1549 represents a genuine transposon capable of forming a circular intermediate in order to be transferred and integrated into the target bacterial chromosome in the gut of gnotobiotic mice[10]. Contradicting these results, in vitro experiments performed by Quintiliani, Carias, and others show the movement of large chromosomal elements which would favor a mechanism related to homologous or illegitimate recombination[11,12,13,14]. As vanB-positive E. faecium ST192 led to a marked increase of VRE outbreaks and became a highly prevalent lineage of bloodstream infections in Germany in recent years, the present study was conducted to investigate VRE of this particular sequence type with respect to i) population structure, ii) acquisition of the vanB resistance determinant and iii) transfer of the resistance locus

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Conclusion