Genomic epidemiology of vancomycin resistantEnterococcus faecium(VREfm) in Latin America: Revisiting the global VRE population structure

Abstract

42The prevalence of vancomycin-resistant Enterococcus faecium varies across 43 geographical regions yet little is known about its population structure in Latin 44 America. Here, we provide a complete genomic characterization of 55 45 representative Latin American VREfm recovered from 1998-2015 in 5 countries. 46 We found that VREfm population in the region is structured into two main clinical 47 clades without geographical clustering. To place our regional findings in context, 48 we reconstructed the global population structure of VREfm by including 285 49 genomes from 36 countries from 1946-2017. Our results differ from previous 50 studies showing an early branching of animal related isolates and a further split of 51 clinical isolates into two sub-clades, all within clade A. The overall phylogenomic 52 structure was highly dependent on recombination (54% of the genome) and the 53 split between clades A and B is estimated to have occurred more than 3585 years 54 BP. Furthermore, while the branching of animal isolates and clinical clades was 55 predicted to have occur ~894 years BP, our molecular clock calculations suggest 56 that the split within the clinical clade occurred around ~371 years BP. By including 57 isolates from Latin America, we present novel insights into the population structure 58 of VREfm and revisit the evolution of this pathogen. 59 60 61 62 63 64 Enterococci are predominantly non-pathogenic gastrointestinal commensal 65 bacteria that occasionally cause human infections. Among them, Enterococcus 66 faecalis and Enterococcus faecium represent the species that account for most 67 clinically relevant infections. In particular, E. faecium has been able to adapt to the 68 hospital environment, emerging during the last few decades as a leading cause of 69 health-care infections worldwide, and becoming the most challenging species to 70 treat 1,2 . 71 Genome plasticity, the presence of multiple antibiotic resistance determinants, and 72 the lack of therapeutic options have contributed to the adaptation of E. faecium to 73 hospital environments 3,4 . Moreover, high recombination rates and the acquisition of 74 mobile elements in the genome of E. faecium also have driven this evolutionary 75 process 5 . In addition, the enrichment of virulence determinants, such as surface 76 proteins and phosphotransferase systems (particularly PTS clin , a putative factor 77 found to contribute to the intestinal colonization in a murine model) seems to 78 provide an advantage to the hospital adaptive process 3,6 . Furthermore, functional 79 gene groups, such as those involved in galactosamine metabolism, bile hydrolysis 80 and phosphorus utilization, are also abundant in E. faecium clinical strains 81 compared to non-clinical isolates, suggesting that specific metabolic factors have 82 also facilitated adaptation 7 .83In terms of antibiotic resistance, one of the most relevant antibiotic resistance traits 84 acquired by enterococci is resistance to vancomycin due to the van gene clusters 8 . 85Furthermor...

Enterococci, from Harmless Bacteria to a Pathogen

“…In the U.S., colonization of hospitalized patients with VRE rapidly increased since the first VRE detection, up to the current endemic levels in many hospitals. On the contrary, in Europe, the prevalence rates in hospitals have remained much lower and only started to increase since the year 2000 [17,20]. The initial reports of VRE in Europe were of organisms that were frequently isolated from healthy people, farm animals, pets, and retail food products, suggesting a large community reservoir [14,21], whereas such a community reservoir seemed absent in the US.…”