Retrospective analysis of genome sequences revealed the wide dissemination of
            <i>optrA</i>
            in Gram-positive bacteria

Huang, Jinhu; Chen, Li; Wu, Zhongliang; Wang, Liping

doi:10.1093/jac/dkw488

Cited by 56 publications

(39 citation statements)

References 9 publications

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“…Strains originating from the same source or country were dispersed across the different tree branches, suggesting no significant correlation between strain origin and phylogeny as commonly observed in E. faecalis [31]. These results further confirm the easy promiscuity of optrA that has been identified in enterococci from highly variable epidemiological and genetic backgrounds [2, 32]. The exceptions corresponded to specific strains originating both temporally and locally from the same scenario namely the clinical isolates Iso1Bar/Iso2Bar/Iso3Bar (15-35 SNPs) or Iso4Bar/Iso5Bar (69 SNPs) from an hospital in Barcelona, and the chicken meat isolates 12E/34E (48 SNPs) from Colombia, with close clonal relationships as recently described [12, 22].…”

Section: Resultssupporting

confidence: 68%

“…no. WP_029876135.1), a species previously recognized as a reservoir of optrA [32]. healthy humans (China, Malaysia) and food-producing animals (China, Malaysia, Tunisia) isolates across different continents during 2012-2018.…”

Section: Resultsmentioning

confidence: 99%

“…Considering the finding of optrA embedded in so many diverse genetic platforms amongst different Gram-positive genera (enterococci, staphylococci, streptococci), one can also speculate about the possible optrA mobilization through phage-mediated transduction. Indeed, optrA has already been found as integrated into a larger Fm46.1 prophage (originally from S. pyogenes ) in Streptococcus suis pig isolates [32, 65]. Moreover, Wang et al .…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Comparative genomics of globaloptrA-carryingEnterococcus faecalisuncovers common genetic features and a chromosomal hotspot foroptrAacquisition

Freitas

Tedim

Novais

et al. 2019

Preprint

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27Linezolid-resistant Enterococcus faecalis (LREfs) carrying optrA are increasingly reported globally 28 from multiple sources, but we still lack a comprehensive analysis of human and animal optrA-LREfs 29 strains. We investigated the phylogenetic structure, genetic content [antimicrobial resistance (AMR), 30 virulence, prophages, plasmidome] and optrA-containing platforms of 28 publicly available optrA-31 positive E. faecalis genomes from different hosts in 7 countries. In the genome-level analysis, in house 32 databases with 57 virulence and 391 plasmid replication genes were tested for the first time. Our 33 analysis showed a diversity of clones and adaptive gene sequences related to a wide range of genera, 34 mainly but not exclusive from Firmicutes. The content in AMR and virulence genes was highly 35identical in contrast to the diversity of phages and plasmids observed. Epidemiologically unrelated 36 clones (ST476-like and ST21-like) obtained from human clinical and animal hosts in different 37 continents over 5 years (2012)(2013)(2014)(2015)(2016)(2017) were phylogenetically related (3-122 SNPs difference). They also 38 exhibited identical AMR and virulence profiles, highlighting a global spread of optrA-positive strains 39 with relevant adaptive traits in livestock and that they might originate from an animal reservoir. optrA 40 was located on the chromosome within a Tn6674-like element (n=9) or on medium-size plasmids (30-41 60 kb; n=14) belonging to main plasmid families (RepA_N/Inc18/Rep_3). In most cases, the 42 immediate gene vicinity of optrA was identical in chromosomal (Tn6674) and plasmid (impB-fexA-43 optrA) backbones. Tn6674 was always inserted in the same ∆radC integration site and embedded in a 44 32 kb chromosomal platform common to diverse strains from different origins (patients, healthy 45 humans, and animals) in Europe, Africa, and Asia during 2012-2018. This platform is conserved 46 among hundreds of E. faecalis genomes and we here propose a conserved chromosomal hotspot for 47 optrA integration. The finding of optrA in strains sharing identical adaptive features and genetic 48 backgrounds across different hosts and countries suggest the occurrence of common and independent 49 genetic events occurring in distant regions, and might explain the easy de novo generation of optrA-50 positive strains. It also anticipates a dramatic increase of optrA carriage and spread with a serious 51 impact in the efficacy of linezolid for the treatment of Gram-positive infections. 52 53 Oxazolidinones (linezolid and tedizolid) are increasingly used for the treatment of human 55 infections caused by relevant pathogens such as methicillin-resistant Staphylococcus aureus and 56 vancomycin-resistant enterococci [1, 2]. Linezolid resistance rates remain generally low in enterococci 57 causing infections worldwide (<1%) [1, 3], however acquired linezolid resistance genes (cfr, optrA 58 and/or poxtA) are being increasingly reported in different enterococcal species and across different 59 settings [2-7]. Among t...

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Section: Resultssupporting

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Comparative genomics of globaloptrA-carryingEnterococcus faecalisuncovers common genetic features and a chromosomal hotspot foroptrAacquisition

Freitas

Tedim

Novais

et al. 2019

Preprint

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“…Three E. faecium isolates from New Orleans and Atlanta also carried the cfr variant cfr(B) (9); note that the newly described transferable optrA gene was found in 2 E. faecalis isolates from Vermont and Wisconsin in 2014 to 2015. This gene was first reported in enterococci from China in 2015 (16) and has been detected since then in human clinical specimens from several continents (8,(20)(21)(22)(23)(24). Linezolid showed uniform potency against the 2015 collection of Streptococcus pneumoniae (MIC 50/90 , 1/1 g/ml), viridans group streptococci (MIC 50/90 , 0.5/1 g/ml), and beta-hemolytic streptococci (MIC 50/90 , 1/1 g/ml) ( Tables 2 and 3).…”

Section: Isolates) S Pseudintermedius/s Intermedius/s Delphini (1mentioning

confidence: 94%

Five-Year Summary of In Vitro Activity and Resistance Mechanisms of Linezolid against Clinically Important Gram-Positive Cocci in the United States from the LEADER Surveillance Program (2011 to 2015)

Pfaller

Mendes

Streit

et al. 2017

Antimicrob Agents Chemother

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This report describes linezolid susceptibility testing results for 6,741 Gram-positive pathogens from 60 U.S. sites collected during 2015 for the LEADER Program. In addition, the report summarizes linezolid in vitro activity, resistance mechanisms, and molecular typing obtained for 2011 to 2015. During 2015, linezolid showed potent activity in testing against Staphylococcus aureus, inhibiting Ͼ99.9% of 3,031 isolates at Յ2 g/ml. Similarly, linezolid showed coverage against 99.2% of coagulase-negative staphylococci, 99.7% of enterococci, and 100.0% of Streptococcus pneumoniae, virdans group, and beta-hemolytic streptococcus isolates tested. The overall linezolid resistance rate remained a modest Ͻ1% from 2011 to 2015. Staphylococci, especially Staphylococcus epidermidis, showed a range of linezolid resistance mechanisms. Increased annual trends for the presence of cfr among Staphylococcus aureus isolates were not observed, but 64.3% (9/14) of the isolates with decreased susceptibility (MIC, Ն4 g/ml) to linezolid carried this transferrable gene (2011 to 2015). The cfr gene was detected in 21.9% (7/32) of linezolid-resistant staphylococci other than S. aureus from 2011 to 2015. The optrA gene was noted in half (2/4) of the population of linezolid-nonsusceptible Enterococcus faecalis isolates from 2011 to 2015, while linezolid-nonsusceptible Enterococcus faecium isolates showed alterations predominantly (16/16) in the 23S rRNA gene (G2576T). This report confirms a long record of linezolid activity against Gram-positive isolates in the United States since regulatory approval in 2000 and reports the oxazolidinones evolving resistance mechanisms.

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“…The optrA -carrying plasmids in enterococci have also other AMR-genes against antibiotics such as MLS B [ erm (A)-like)] and/or phenicol ( fexA ) [40]. Retrospective analysis of genome sequences has revealed that optrA has a wide dissemination in Gram-positive bacteria and it has also been found in diverse Streptococcus species (including S. suis , S. agalactiae and S. pyogenes ) [69]. …”

Section: Amr-genes In Gram-positive Bacteria From Animalsmentioning

confidence: 99%

Bacteria from Animals as a Pool of Antimicrobial Resistance Genes

et al. 2017

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Antimicrobial agents are used in both veterinary and human medicine. The intensive use of antimicrobials in animals may promote the fixation of antimicrobial resistance genes in bacteria, which may be zoonotic or capable to transfer these genes to human-adapted pathogens or to human gut microbiota via direct contact, food or the environment. This review summarizes the current knowledge of the use of antimicrobial agents in animal health and explores the role of bacteria from animals as a pool of antimicrobial resistance genes for human bacteria. This review focused in relevant examples within the ESC(K)APE (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile (Klebsiella pneumoniae), Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae) group of bacterial pathogens that are the leading cause of nosocomial infections throughout the world.

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Retrospective analysis of genome sequences revealed the wide dissemination of optrA in Gram-positive bacteria

Cited by 56 publications

References 9 publications

Comparative genomics of globaloptrA-carryingEnterococcus faecalisuncovers common genetic features and a chromosomal hotspot foroptrAacquisition

Comparative genomics of globaloptrA-carryingEnterococcus faecalisuncovers common genetic features and a chromosomal hotspot foroptrAacquisition

Five-Year Summary of In Vitro Activity and Resistance Mechanisms of Linezolid against Clinically Important Gram-Positive Cocci in the United States from the LEADER Surveillance Program (2011 to 2015)

Bacteria from Animals as a Pool of Antimicrobial Resistance Genes

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