Nationwide Surveillance of Novel Oxazolidinone Resistance Gene
            <i>optrA</i>
            in Enterococcus Isolates in China from 2004 to 2014

Cui, Lanqing; Wang, Yang; Lv, Yuan; Wang, Shan; Song, Yunjia; Li, Yun; Liu, Jian; Xue, Feng; Yang, Weiwei; Zhang, Jia

doi:10.1128/aac.01256-16

Cited by 63 publications

(53 citation statements)

References 14 publications

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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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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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“…Curcumin and related compounds are credited with a wide spectrum of biological activities. [1] Numerous studies have shown that curcumin possess antiinflammatory, [2] antioxidant, [3] antitumor, [4] antimalarial, [5] and analogues included Ph, m-MeO-C 6 H 4 , 3,4-di-MeO-C 6 H 3 , 3,4,5-tri-MeO-C 6 H 2 , p-Br-C 6 H 4 , p-F-C 6 H 4 , p-CF 3 many other biological activities. [6] Despite its broad spectrum of activities and good safety profile curcumin is hard to develop as a drug because of its poor oral bioavailability.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Dicarbonyl Curcumin Analogues Containing the Tropane Scaffold

et al. 2019

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A general synthetic route to the unknown 1,3‐dicarbonyl tropane derived curcumin analogues was developed. The method was based on the aldol condensation reaction (40–90 % yield, two steps without product isolation) and acylation of the resulting 2‐benzylidenetropinones with substituted cinnamoyl cyanides (yields 41–91 %). Overall 18 new tropane derivatives featuring the characteristic curcuminoid hepta‐1,6‐dien‐3,5‐dione structure were synthesized and characterized. The range of the substituted aromatic rings in the prepared analogues included Ph, m‐MeO‐C6H4, 3,4‐di‐MeO‐C6H3, 3,4,5‐tri‐MeO‐C6H2, p‐Br‐C6H4, p‐F‐C6H4, p‐CF3‐C6H4, p‐NO2‐C6H4, 2‐NO2‐4,5‐di‐CH3O‐C6H2, 2‐NO2‐4,5‐O‐CH2‐O‐C6H2, 3‐MeO‐4‐[CH(CH3)‐OEt]‐C6H3, 3‐MeO‐4‐OH‐C6H3, p‐MeO‐C6H4, 4,5‐O‐CH2‐O‐C6H3, 3‐MeO‐4‐MeOCOO. Two orthogonal protective groups for hydroxyl (acetal or carbonate), removable in acidic or basic conditions, were used for synthesizing curcuminoids with free phenolic groups (3‐MeO‐4‐OH‐C6H3).

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“…While this mechanism of linezolid resistance in E. faecium and S. au-reus is predominant in Korea, resistance due to variants in ribosomal proteins L3, L4, and L22 have also been reported [3]. Acquisition of the linezolid resistance gene cfr or, more recently, optrA is more threatening because these genes are plasmid encoded and, thus, transmissible [4]. Human isolates of optrApositive linezolid-nonsusceptible Enterococcus faecalis (LNSEF) were reported first in 2016 in China [4] and later in the USA, Sweden, France, Thailand, Taiwan, Malaysia, and Korea [3,5].…”

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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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Nationwide Surveillance of Novel Oxazolidinone Resistance Gene optrA in Enterococcus Isolates in China from 2004 to 2014

Cited by 63 publications

References 14 publications

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

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

Synthesis of Dicarbonyl Curcumin Analogues Containing the Tropane Scaffold

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

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