Emergence of optrA-mediated linezolid resistance in enterococci from France, 2006–16

Sassi, Mohamed; Guérin, François; Zouari, Asma; Beyrouthy, Racha; Auzou, Michel; Fines-Guyon, Marguerite; Potrel, Sophie; Dejoies, Loren; Collet, Anaïs; Boukthir, Sarrah; Auger, Gabriel; Bonnet, Richard; Cattoir, Vincent

doi:10.1093/jac/dkz097

Cited by 54 publications

(31 citation statements)

References 19 publications

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“…First, we detected a high prevalence of plasmid-borne optrA gene in E. faecalis clinical isolates. The proportion of isolates carrying optrA in the plasmid was slightly higher isolates carrying optrA in the chromosome (59% vs 41%), which is consistent with previous reports in China (13, 15) and other countries (6, 22, 37). Location of the resistance gene is a plasmid is known to enable fast and efficient gene transfer within and between different bacterial host species.…”

Section: Discussionsupporting

confidence: 92%

“…OptrA encodes the ATP-binding cassette F (ABC-F) protein family and mediates resistance to phenicols and oxazolidinones through protection of the bacterial ribosome from antibiotic inhibition (13, 14). Following the first report of the optrA gene in 2015 from an E. faecalis isolate obtained from a blood sample of a Chinese patient (13), optrA has been found worldwide not only in E. faecalis and E. faecium (15–22) but also in other Gram-positive bacteria such as Staphylococcus sciuri (23, 24) and Streptococcus suis (25). In addition, optrA has been detected not only in various human clinical samples but also in diverse livestock samples such as cow milk, faeces or meat from pigs, chicken and ducks (26, 27) as well as environmental samples such as soils (28) and urban wastewater (29).…”

Section: Introductionmentioning

confidence: 99%

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Dissemination of linezolid-resistance through sex pheromone plasmid transfer in Enterococcs faecalis

Zou

Tang

Jia

et al. 2019

Preprint

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24Despite recent recognition of the ATP-binding cassette protein OptrA as an important mediator of 25 linezolid-resistance in Enterococcus faecalis worldwide, the mechanisms of optrA gene 26 acquisition and transfer remain poorly understood. In this study, we performed comprehensive 27 molecular and phenotypic profiling of 44 optrA-carrying E. faecalis clinical isolates with 28 linezolid-resistance. Pulse-field gel electrophoresis and DNA hybridization revealed the presence 29 of optrA in the plasmid in 26 (59%) isolates and in the chromosome in 18 (41%) isolates. 30Conjugation experiments showed a successful transfer of optrA in 88.5% (23/26) of isolates 31 carrying optrA in plasmids while no transfer occurred in any isolates carrying optrA in the 32 chromosome (0/18). All 23 transconjugants exhibited in vitro resistance to linezolid and several 33 other antibiotics, and were confirmed to contain optrA and other resistance genes. Plasmid typing 34 demonstrated a predominance (18/23 or 78%) of rep 9 -type plasmids (pCF10 prototype) known to 35 be the best studied sex pheromone responsive plasmids. Full plasmid genome sequencing of one 36 isolate revealed the presence of drug resistance genes (optrA and fexA) and multiple sex 37 pheromone response genes in the same plasmid, which represents the first sex pheromone 38 responsive plasmid carrying optrA from a clinical isolate. PCR-based genotyping revealed the 39 presence of three key sex pheromone response genes (prgA, prgB and prgC) in almost all 23 40 optrA-carrying isolates tested. Finally, functional studies of these isolates by clumping induction 41 assay detected different degrees of clumping in most of the 23 isolates. Our analysis strongly 42 suggests that optrA-mediated linezolid-resistance can be widely disseminated through sex 43 pheromone plasmid transfer. 44 45

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Dissemination of linezolid-resistance through sex pheromone plasmid transfer in Enterococcs faecalis

Zou

Tang

Jia

et al. 2019

Preprint

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“…Linezolid resistance rates remain generally low in enterococci causing infections worldwide (<1 %) [1,3], however, acquired linezolid resistance genes (cfr, optrA and/or poxtA) are being increasingly reported in different enterococcal species and across different settings [2][3][4][5][6][7]. Among the three transferable linezolid resistance genes, optrA has been the main one responsible for the recent increase in linezolid-resistant enterococci (LRE) in human isolates [8][9][10][11][12][13]. According to available studies, optrA-carrying LRE are globally circulating in hospitals since at least 2005 [14], while the first description in food-producing animals dates from 2008 [15].…”

Section: Introductionmentioning

confidence: 99%

Comparative genomics of global optrA-carrying Enterococcus faecalis uncovers a common chromosomal hotspot for optrA acquisition within a diversity of core and accessory genomes

et al. 2020

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Linezolid-resistant Enterococcus faecalis (LREfs) carrying optrA are increasingly reported globally from multiple sources, but we lack a comprehensive analysis of human and animal optrA-LREfs strains. To assess if optrA is dispersed in isolates with varied genetic backgrounds or with common genetic features, we investigated the phylogenetic structure, genetic content [antimicrobial resistance (AMR), virulence, prophages, plasmidome] and optrA-containing platforms of 27 publicly available optrA-positive E. faecalis genomes from different hosts in seven countries. At the genome-level analysis, an in-house database with 64 virulence genes was tested for the first time. Our analysis showed a diversity of clones and adaptive gene sequences related to a wide range of genera from Firmicutes . Phylogenies of core and accessory genomes were not congruent, and at least PAI-associated and prophage genes contribute to such differences. Epidemiologically unrelated clones (ST21, ST476-like and ST489) obtained from human clinical and animal hosts in different continents over eight years (2010–2017) could be phylogenetically related (3–126 SNPs difference). optrA was located on the chromosome within a Tn6674-like element (n=10) 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 optrA was generally identical in chromosomal (Tn6674) or plasmid (impB-fexA-optrA) backbones. Tn6674 was always inserted into the same ∆radC integration site and embedded in a 32 kb chromosomal platform common to strains from different origins (patients, healthy humans, and animals) in Europe, Africa, and Asia during 2012–2017. This platform is conserved among hundreds of E. faecalis genomes and proposed as a chromosomal hotspot for optrA integration. The finding of optrA in strains sharing common adaptive features and genetic backgrounds across different hosts and countries suggests the occurrence of common and independent genetic events occurring in distant regions and might explain the easy de novo generation of optrA-positive strains. It also anticipates a dramatic increase of optrA carriage and spread with a serious impact on the efficacy of linezolid for the treatment of Gram-positive infections.

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“…ST585 strains harboring optrA have been reported in the USA, China, and Germany [5,10,13]. ST480 strains harboring optrA have been reported in China, France, Germany, and Belgium [12][13][14][15]. Studies in China have revealed that optrA is more prevalent in animal enterococcal isolates (15.9%) than human isolates (2.0%) [10] and that 3.5% of healthy individuals carry optrA-carrying E. faecalis, regardless of age [16].…”

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confidence: 99%

Emergence of optrA-Mediated Linezolid-Nonsusceptible Enterococcus faecalis in a Tertiary Care Hospital

et al. 2020

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This study investigated resistance mechanisms and epidemiology of emerging linezolidnonsusceptible Enterococcus faecalis (LNSEF) in a tertiary care hospital. LNSEF isolated from clinical samples were collected from November 2017 to June 2019. The isolates were investigated for linezolid resistance and the associated molecular mechanisms, including mutations of 23S rRNA domain V and acquisition of the cfr or optrA resistance gene. We used pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing for the molecular typing of the isolates. Among 4,318 E. faecalis isolates, 10 (0.23%) were linezolid-nonsusceptible. All LNSEF isolates were optrA-positive and cfr-negative. Of these isolates, five were sequence type (ST) 476, two ST585, one ST16, one ST16-like, and one ST480. Six LNSEF isolates obtained in the first year clustered to three types in the PFGE analysis: two ST476 isolates of type A, two ST585 isolates of type B, and two ST16 or ST16-like isolates of type C. Seven cases were of community-onset and three were hospital acquired, but total of eight were healthcare-associated including five community-onset. None of the patients had a history of linezolid treatment, and in one patient, we detected linezolid-susceptible E. faecalis one month before LNSEF detection. In conclusion, heterogenous clones of optrA-positive LNSEF emerged in the hospital mainly via communityonset. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Emergence of optrA-mediated linezolid resistance in enterococci from France, 2006–16

Cited by 54 publications

References 19 publications

Dissemination of linezolid-resistance through sex pheromone plasmid transfer in Enterococcs faecalis

Dissemination of linezolid-resistance through sex pheromone plasmid transfer in Enterococcs faecalis

Comparative genomics of global optrA-carrying Enterococcus faecalis uncovers a common chromosomal hotspot for optrA acquisition within a diversity of core and accessory genomes

Emergence of optrA-Mediated Linezolid-Nonsusceptible Enterococcus faecalis in a Tertiary Care Hospital

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