Comparative genomics of global optrA-carrying Enterococcus faecalis uncovers common genetic features and a chromosomal hotspot for optrA acquisition

• Type: Other Publications
• Date: 2019

Authors

Freitas, AR (Author) Other; Tedim, AP (Author) Other; Novais, Carla (Author) FFUP; Luisa Peixe (Author) FFUP

Other information

Authenticus ID: P-00S-6MK

DOI: 10.1101/785295

Abstract (EN): <jats:title>Abstract</jats:title><jats:p>Linezolid-resistant <jats:italic>Enterococcus faecalis</jats:italic> (LREfs) carrying <jats:italic>optrA</jats:italic> are increasingly reported globally from multiple sources, but we still lack a comprehensive analysis of human and animal <jats:italic>optrA</jats:italic>-LREfs strains. We investigated the phylogenetic structure, genetic content [antimicrobial resistance (AMR), virulence, prophages, plasmidome] and <jats:italic>optrA</jats:italic>-containing platforms of 28 publicly available <jats:italic>optrA</jats:italic>-positive <jats:italic>E. faecalis</jats:italic> genomes from different hosts in 7 countries. In the genome-level analysis, <jats:italic>in house</jats:italic> databases with 57 virulence and 391 plasmid replication genes were tested for the first time. Our analysis showed a diversity of clones and adaptive gene sequences related to a wide range of genera, mainly but not exclusive from <jats:italic>Firmicutes</jats:italic>. The content in AMR and virulence genes was highly identical in contrast to the diversity of phages and plasmids observed. Epidemiologically unrelated clones (ST476-like and ST21-like) obtained from human clinical and animal hosts in different continents over 5 years (2012-2017) were phylogenetically related (3-122 SNPs difference). They also exhibited identical AMR and virulence profiles, highlighting a global spread of <jats:italic>optrA</jats:italic>-positive strains with relevant adaptive traits in livestock and that they might originate from an animal reservoir. <jats:italic>optrA</jats:italic> was located on the chromosome within a Tn<jats:italic>6674</jats:italic>-like element (n=9) or on medium-size plasmids (30-60 kb; n=14) belonging to main plasmid families (RepA_N/Inc18/Rep_3). In most cases, the immediate gene vicinity of <jats:italic>optrA</jats:italic> was identical in chromosomal (Tn<jats:italic>6674</jats:italic>) and plasmid (<jats:italic>impB-fexA-optrA</jats:italic>) backbones. Tn<jats:italic>6674</jats:italic> was always inserted in the same ¿<jats:italic>radC</jats:italic> integration site and embedded in a 32 kb chromosomal platform common to diverse strains from different origins (patients, healthy humans, and animals) in Europe, Africa, and Asia during 2012-2018. This platform is conserved among hundreds of <jats:italic>E. faecalis</jats:italic> genomes and we here propose a conserved chromosomal hotspot for <jats:italic>optrA</jats:italic> integration. The finding of <jats:italic>optrA</jats:italic> in strains sharing identical adaptive features and genetic backgrounds across different hosts and countries suggest the occurrence of common and independent genetic events occurring in distant regions, and might explain the easy <jats:italic>de novo</jats:italic> generation of <jats:italic>optrA</jats:italic>-positive strains. It also anticipates a dramatic increase of <jats:italic>optrA</jats:italic> carriage and spread with a serious impact in the efficacy of linezolid for the treatment of Gram-positive infections.</jats:p>

Language: English

Type (Professor's evaluation): Scientific