Comparative Genomic Analysis of Enterococci across Sectors of the One Health Continuum

Abstract

Enterococci are Gram-positive bacteria that can be isolated from a variety of environments including soil, water, plants, and the intestinal tract of humans and animals. Although they are considered commensals in humans, Enterococcus spp. are important opportunistic pathogens. Due to their presence and persistence in diverse environments, Enterococcus spp. are ideal for studying antimicrobial resistance (AMR) from the One Health perspective. We undertook a comparative genomic analysis of the virulome, resistome, mobilome, and the association between the resistome and mobilome of 246 E. faecium and 376 E. faecalis recovered from livestock (swine, beef cattle, poultry, dairy cattle), human clinical samples, municipal wastewater, and environmental sources. Comparative genomics of E. faecium and E. faecalis identified 31 and 34 different antimicrobial resistance genes (ARGs), with 62% and 68% of the isolates having plasmid-associated ARGs, respectively. Across the One Health continuum, tetracycline (tetL and tetM) and macrolide resistance (ermB) were commonly identified in E. faecium and E. faecalis. These ARGs were frequently associated with mobile genetic elements along with other ARGs conferring resistance against aminoglycosides [ant(6)-la, aph(3′)-IIIa], lincosamides [lnuG, lsaE], and streptogramins (sat4). Study of the core E. faecium genome identified two main clades, clade ‘A’ and ‘B’, with clade A isolates primarily originating from humans and municipal wastewater and carrying more virulence genes and ARGs related to category I antimicrobials. Overall, despite differences in antimicrobial usage across the continuum, tetracycline and macrolide resistance genes persisted in all sectors.

Dissemination of Enterococcal Genetic Lineages: A One Health Perspective

“…AMR refers to the ability of bacterial cells to withstand and avoid the harmful effects of antimicrobial agents [36], leading to difficulties in treating infections caused by resistant bacteria. As opportunistic pathogens, enterococci initially caused infections in immunocompromised patients, and later gained relevance as a major pathogen in hospitals with the introduction of third-generation cephalosporins (β-lactams class), to which these bacteria are naturally resistant [3].…”

“…Accordingly, antimicrobial resistance and the dissemination of resistance genes through interconnected ecosystems have been considered quintessential One Health issues [53]. To face this problem, many authors [18,36,38,54,55] have been performing comparative genomic analyses of Enterococcus spp. as indicator bacteria, to study the transference of ARGs, virulence genes, and MGE determinants across the One Health continuum.…”

“…Many authors [18,36,38,97] have been focusing on the interplay between human, animal, community, and environmental enterococcal clones, from a One Health perspective. Nevertheless, to the best of our knowledge, no review has provided a roadmap of the clonal spread from human clinical settings to animals, food, the community, and the environment, highlighting the dissemination not only between sectors but also around the globe, as hereby presented.…”

“…Nevertheless, the authors [18] found association between specific gene profiles and MGEs with the habitat and pointed out the possibility of enterococcal pathogenicity features being associated with a group of clinical/municipal wastewater genomes, which might constitute a human-associated ecotype within clade A. Recently, a One Health comparative genomic analysis of virulome, resistome, and mobilome in E. faecium and E. faecalis isolated from livestock, human clinical samples, municipal wastewater, and other environmental sources was performed [36].…”

“…The study [36] identified 31 E. faecium and 34 E. faecalis ARGs (62 and 68% being plasmidassociated, respectively), with tetracycline (tetL and tetM, frequently found on pM7M2) and macrolide (ermB) resistance being described in all sectors of the One Health continuum. Additionally, Noh et al [152] also observed the presence of tetM, ermA, and ermB genes in virulent-MDR E. faecalis strains recovered from poultry in Korea, highlighting the spread of tetracycline and macrolide resistance genes among enterococcal isolates from various sectors.…”