Genomic Epidemiology of Vancomycin-Resistant Enterococcus faecium (VREfm) in Latin America: Revisiting The Global VRE Population Structure

Rafael Rios,Lorena Diaz,Cesar A Arias,Diana Panesso,Jinnethe Reyes,Lina P Carvajal,Paul J Planet,Apurva Narechania,Sergios-Orestis Kolokotronis,An Dinh,Barbara E Murray,Aura M Echeverri,Sandra Rincon,Jose M Munita,Truc T Tran

doi:10.1038/s41598-020-62371-7

Abstract

Little is known about the population structure of vancomycin-resistant Enterococcus faecium (VREfm) in Latin America (LATAM). Here, we provide a complete genomic characterization of 55 representative Latin American VREfm recovered from 1998–2015 in 5 countries. The LATAM VREfm population is structured into two main clinical clades without geographical clustering. Using the LATAM genomes, we reconstructed the global population of VREfm by including 285 genomes from 36 countries spanning from 1946 to 2017. In contrast to previous studies, our results show an early branching of animal related isolates and a further split of clinical isolates into two sub-clades within clade A. The overall phylogenomic structure of clade A was highly dependent on recombination (54% of the genome) and the split between clades A and B was estimated to have occurred more than 2,765 years ago. Furthermore, our molecular clock calculations suggest the branching of animal isolates and clinical clades occurred ~502 years ago whereas the split within the clinical clade occurred ~302 years ago (previous studies showed a more recent split between clinical an animal branches around ~74 years ago). By including isolates from Latin America, we present novel insights into the population structure of VREfm and revisit the evolution of these pathogens.

Highlights

Genome plasticity, the presence of multiple antibiotic resistance determinants and the lack of therapeutic options have contributed to the adaptation of E. faecium to hospital environments[3,4]
In order to characterize the vancomycin-resistant E. faecium (VREfm) lineages circulating in Latin America, we reconstructed their phylogenetic history based on 1,674 genes present in more than 90% of the genome sequences from a total of 6735 orthogroups using a Bayesian approach (Fig. 1A)
We observed that the emergence of VREfm in Colombia was associated with Clade II, including the first VREfm and representatives from the first national surveillance (2001 to 2002)

Summary

Introduction

The presence of multiple antibiotic resistance determinants and the lack of therapeutic options have contributed to the adaptation of E. faecium to hospital environments[3,4]. A further subdivision has been described within clade A, which groups isolates from animal origin in a subclade (designated as A2), separating them from those recovered from human infections or colonization (subclade A1)[3]. These analyses have been performed using mostly US and European isolates, lacking geographical diversity, in areas such as Latin America. Studies analysing the population structure of VREfm in the region using high-resolution, WGS-based phylogenomic comparative methods are limited. We sought to characterize the population structure of VREfm lineages in a collection of isolates recovered between 1998–2015 in prospective multicentre studies performed in selected Latin-American hospitals[14,25,26]. Using the Latin American genomes, we revisit the global population structure and evolutionary history of VREfm

Objectives

Methods

Results

Discussion

Conclusion