Molecular Epidemiology and Genetic Context of optrA-Carrying Linezolid-Resistant Enterococci from Humans and Animals in South Korea
Abstract
:1. Introduction
2. Results
2.1. Prevalence and Antimicrobial Resistance of Linezolid-Resistant Enterococci
2.2. Molecular Typing and Genetic Characteristics of optrA-Positive Isolates
2.3. Genetic Environment and Phylogenetic Relatedness
3. Discussion
4. Materials and Methods
4.1. Bacterial Isolates
4.2. Screening of Linezolid Resistance Genes
4.3. Whole-Genome Sequencing and Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Arias, C.A.; Murray, B.E. The rise of the Enterococcus: Beyond vancomycin resistance. Nat. Rev. Microbiol. 2012, 10, 266–278. [Google Scholar] [CrossRef] [PubMed]
- Bialvaei, A.Z.; Rahbar, M.; Yousefi, M.; Asgharzadeh, M.; Kafil, H.S. Linezolid: A promising option in the treatment of Gram-positives. J. Antimicrob. Chemother. 2016, 72, 354–364. [Google Scholar] [CrossRef] [PubMed]
- Long, K.S.; Poehlsgaard, J.; Kehrenberg, C.; Schwarz, S.; Vester, B. The Cfr rRNA Methyltransferase Confers Resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A Antibiotics. Antimicrob. Agents Chemother. 2006, 50, 2500–2505. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Lv, Y.; Cai, J.; Schwarz, S.; Cui, L.; Hu, Z.; Zhang, R.; Li, J.; Zhao, Q.; He, T.; et al. A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in Enterococcus faecalis and Enterococcus faecium of human and animal origin. J. Antimicrob. Chemother. 2015, 70, 2182–2190. [Google Scholar] [CrossRef]
- Antonelli, A.; D’andrea, M.M.; Brenciani, A.; Galeotti, C.L.; Morroni, G.; Pollini, S.; Varaldo, P.E.; Rossolini, G.M. Characterization of poxtA, a novel phenicol–oxazolidinone–tetracycline resistance gene from an MRSA of clinical origin. J. Antimicrob. Chemother. 2018, 73, 1763–1769. [Google Scholar] [CrossRef]
- Bi, R.; Qin, T.; Fan, W.; Ma, P.; Gu, B. The emerging problem of linezolid-resistant enterococci. J. Glob. Antimicrob. Resist. 2018, 13, 11–19. [Google Scholar] [CrossRef]
- Bender, J.K.; Cattoir, V.; Hegstad, K.; Sadowy, E.; Coque, T.M.; Westh, H.; Hammerum, A.M.; Schaffer, K.; Burns, K.; Murchan, S.; et al. Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: Towards a common nomenclature. Drug Resist. Updat. 2018, 40, 25–39. [Google Scholar] [CrossRef]
- Egan, S.A.; Shore, A.C.; O’connell, B.; Brennan, G.I.; Coleman, D.C. Linezolid resistance in Enterococcus faecium and Enterococcus faecalis from hospitalized patients in Ireland: High prevalence of the MDR genes optrA and poxtA in isolates with diverse genetic backgrounds. J. Antimicrob. Chemother. 2020, 75, 1704–1711. [Google Scholar] [CrossRef]
- Fu, Y.; Deng, Z.; Shen, Y.; Wei, W.; Xiang, Q.; Liu, Z.; Hanf, K.; Huang, S.; Lv, Z.; Cao, T.; et al. High prevalence and plasmidome diversity of optrA-positive enterococci in a Shenzhen community, China. Front. Microbiol. 2024, 15, 1505107. [Google Scholar] [CrossRef]
- Abdullahi, I.N.; Lozano, C.; Zarazaga, M.; Latorre-Fernández, J.; Hallstrøm, S.; Rasmussen, A.; Stegger, M.; Torres, C. Genomic Characterization and Phylogenetic Analysis of Linezolid-Resistant Enterococcus from the Nostrils of Healthy Hosts Identifies Zoonotic Transmission. Curr. Microbiol. 2024, 81, 1–13. [Google Scholar] [CrossRef]
- Freitas, A.R.; Tedim, A.P.; Novais, C.; Lanza, V.F.; Peixe, L. Comparative genomics of global optrA-carrying Enterococcus faecalis uncovers a common chromosomal hotspot for optrA acquisition within a diversity of core and accessory genomes. Microb. Genom. 2020, 6, e000350. [Google Scholar] [CrossRef] [PubMed]
- Li, D.; Li, X.-Y.; Schwarz, S.; Yang, M.; Zhang, S.-M.; Hao, W.; Du, X.-D. Tn 6674 Is a Novel Enterococcal optrA -Carrying Multiresistance Transposon of the Tn 554 Family. Antimicrob. Agents Chemother. 2019, 63. [Google Scholar] [CrossRef] [PubMed]
- Li, P.; Gao, M.; Feng, C.; Yan, T.; Sheng, Z.; Shi, W.; Liu, S.; Zhang, L.; Li, A.; Lu, J.; et al. Molecular characterization of florfenicol and oxazolidinone resistance in Enterococcus isolates from animals in China. Front. Microbiol. 2022, 13, 811692. [Google Scholar] [CrossRef] [PubMed]
- Ministry of Agriculture, Food and Rural Affairs; Animal and Plant Quarantine Agency; Ministry of Food and Drug Safety. National Antibiotic Use and Resistance Monitoring in 2021. Available online: https://impfood.mfds.go.kr/CFBCC02F02/getCntntsDetail?cntntsSn=480817&cntntsMngId=00006 (accessed on 15 November 2022).
- Hu, Y.; Won, D.; Nguyen, L.P.; Osei, K.M.; Seo, Y.; Kim, J.; Lee, Y.; Lee, H.; Yong, D.; Choi, J.R.; et al. Prevalence and Genetic Analysis of Resistance Mechanisms of Linezolid-Nonsusceptible Enterococci in a Tertiary Care Hospital Examined via Whole-Genome Sequencing. Antibiotics 2022, 11, 1624. [Google Scholar] [CrossRef]
- Ha, H.T.A.; Nguyen, P.T.L.; Hung, T.T.M.; Tuan, L.A.; Thuy, B.T.; Lien, T.H.M.; Thai, P.D.; Thanh, N.H.; Bich, V.T.N.; Anh, T.H.; et al. Prevalence and Associated Factors of optrA-Positive-Enterococcus faecalis in Different Reservoirs around Farms in Vietnam. Antibiotics 2023, 12, 954. [Google Scholar] [CrossRef]
- Roy, S.; Aung, M.S.; Paul, S.K.; Khan, M.N.A.; Nasreen, S.A.; Hasan, M.S.; Haque, N.; Barman, T.K.; Khanam, J.; Sathi, F.A.; et al. Isolation of vanA-Mediated Vancomycin-Resistant Enterococcus faecalis (ST1912/CC116) and Enterococcus faecium (ST80/CC17), optrA-Positive Linezolid-Resistant E. faecalis (ST32, ST1902) from Human Clinical Specimens in Bangladesh. Antibiotics 2025, 14, 261. [Google Scholar] [CrossRef]
- Mortelé, O.; Koeveringe, S.v.K.; Vandamme, S.; Jansens, H.; Goossens, H.; Matheeussen, V. Epidemiology and genetic diversity of linezolid-resistant Enterococcus clinical isolates in Belgium from 2013 to 2021. J. Glob. Antimicrob. Resist. 2024, 38, 21–26. [Google Scholar] [CrossRef]
- Argudín, M.A.; Youzaga, S.; Dodémont, M.; Heinrichs, A.; Roisin, S.; Deplano, A.; Nonhoff, C.; Hallin, M. Detection of optrA-positive enterococci clinical isolates in Belgium. Eur. J. Clin. Microbiol. Infect. Dis. 2019, 38, 985–987. [Google Scholar] [CrossRef]
- Egan, S.; Corcoran, S.; McDermott, H.; Fitzpatrick, M.; Hoyne, A.; McCormack, O.; Cullen, A.; Brennan, G.; O’Connell, B.; Coleman, D. Hospital outbreak of linezolid-resistant and vancomycin-resistant ST80 Enterococcus faecium harbouring an optrA-encoding conjugative plasmid investigated by whole-genome sequencing. J. Hosp. Infect. 2020, 105, 726–735. [Google Scholar] [CrossRef]
- Kent, A.G.; Spicer, L.M.; Campbell, D.; Breaker, E.; McAllister, G.A.; Ewing, T.O.; Longo, C.; Balbuena, R.; Burroughs, M.; Burgin, A.; et al. Sentinel Surveillance reveals phylogenetic diversity and detection of linear plasmids harboring vanA and optrA among enterococci collected in the United States. Antimicrob. Agents Chemother. 2024, 68, e0059124. [Google Scholar] [CrossRef]
- Brenciani, A.; Cinthi, M.; Coccitto, S.N.; Massacci, F.R.; Albini, E.; Cucco, L.; Paniccià, M.; Freitas, A.R.; Schwarz, S.; Giovanetti, E.; et al. Global spread of the linezolid-resistant Enterococcus faecalis ST476 clonal lineage carrying optrA. J. Antimicrob. Chemother. 2024, 79, 846–850. [Google Scholar] [CrossRef] [PubMed]
- Albini, E.; Coccitto, S.N.; Cinthi, M.; Giovanetti, E.; Gobbi, M.; Massacci, F.R.; Pavone, S.; Magistrali, C.F.; Brenciani, A. optrA-mediated linezolid resistance in an Enterococcus faecalis isolate recovered from a wild raptor (Falco peregrinus peregrinus), central Italy. J. Glob. Antimicrob. Resist. 2022, 32, 48–49. [Google Scholar] [CrossRef] [PubMed]
- McHugh, M.P.; Parcell, B.J.; Pettigrew, K.A.; Toner, G.; Khatamzas, E.; el Sakka, N.; Karcher, A.M.; Walker, J.; Weir, R.; Meunier, D.; et al. Presence of optrA-mediated linezolid resistance in multiple lineages and plasmids of Enterococcus faecalis revealed by long read sequencing. Microbiology 2022, 168, 001137. [Google Scholar] [CrossRef] [PubMed]
- Gargis, A.S.; Spicer, L.M.; Kent, A.G.; Zhu, W.; Campbell, D.; McAllister, G.; Ewing, T.O.; Albrecht, V.; Stevens, V.A.; Sheth, M.; et al. Sentinel Surveillance Reveals Emerging Daptomycin-Resistant ST736 Enterococcus faecium and Multiple Mechanisms of Linezolid Resistance in Enterococci in the United States. Front. Microbiol. 2022, 12, 807398. [Google Scholar] [CrossRef]
- Lee, H.; Yoon, E.-J.; Kim, D.; Jeong, S.H.; Shin, J.H.; Shin, J.H.; Shin, K.S.; Kim, Y.A.; Uh, Y.; Park, C.; et al. Establishment of the South Korean national antimicrobial resistance surveillance system, Kor-GLASS, in 2016. Eurosurveillance 2018, 23, 9–16. [Google Scholar] [CrossRef]
- Wick, R.R.; Judd, L.M.; Gorrie, C.L.; Holt, K.E. Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput. Biol. 2017, 13, e1005595. [Google Scholar] [CrossRef]
- Seemann, T. Prokka: Rapid Prokaryotic Genome Annotation. Bioinformatics 2014, 30, 2068–2069. [Google Scholar] [CrossRef]
- Alcock, B.P.; Raphenya, A.R.; Lau, T.T.Y.; Tsang, K.K.; Bouchard, M.; Edalatmand, A.; Huynh, W.; Nguyen, A.-L.V.; Cheng, A.A.; Liu, S.; et al. CARD 2020: Antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res. 2020, 48, D517–D525. [Google Scholar] [CrossRef]
- Gardner, S.N.; Slezak, T.; Hall, B.G. kSNP3.0: SNP detection and phylogenetic analysis of genomes without genome alignment or reference genome. Bioinformatics 2015, 31, 2877–2878. [Google Scholar] [CrossRef]
- Argimón, S.; AbuDahab, K.; Goater, R.J.E.; Fedosejev, A.; Bhai, J.; Glasner, C.; Feil, E.J.; Holden, M.T.G.; Yeats, C.A.; Grundmann, H.; et al. Microreact: Visualizing and sharing data for genomic epidemiology and phylogeography. Microb. Genom. 2016, 2, e000093. [Google Scholar] [CrossRef]
Strain | Isolation (Data, Location) | Origin | Specimen | ST | van Operon | Acquired LinezolidResistance Gene | 23S rRNA Mutation | MIC (mg/L) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
optrAa | cfr | poxtA | LZD | VAN | TEC | CHL | DAP | TGC | |||||||
E. faecalis E0017EF0053 | December 2017, Jeolla | Human | Blood | 476 | - | + (c) | - | - | - | 8 | 1 | <0.125 | 32 | 1 | 0.025 |
E. faecalis F0017EF0017 | July 2017, Gyeongsang | Human | Blood | 330 | - | + (p) | - | - | - | 8 | 1 | <0.125 | 64 | 2 | 0.25 |
E. faecalis Z0217EF0166 | September 2017, Jeolla | Pig | Nasal swab | 256 | - | + (c) | - | + | - | >16 | 1 | <0.25 | 16 | 1 | 0.25 |
E. faecalis Z0217EF0167 | September 2017, Jeolla | Pig | Skin | 256 | - | + (c) | - | + | - | >16 | 2 | <0.25 | >64 | 1 | 0.25 |
E. faecalis Z0217EF0171 | September 2017, Jeolla | Pig | Skin | 256 | - | + (c) | - | + | - | >16 | 1 | <0.25 | >64 | 2 | 0.25 |
E. faecalis Z0218EM0045 | Jun 2018, Gyeongsang | Cattle | Skin | 256 | - | + (c) | - | - | - | 8 | 1 | <0.25 | >64 | 1 | 0.25 |
E. faecium Z0219EM0037 | April 2019, Jeolla | Chicken | Rectal swab | 12 | - | + (c) | - | - | - | 8 | 1 | <0.25 | 64 | 4 | 0.125 |
E. faecium Z0219EM0038 | April 2019, Jeolla | Chicken | Skin | 124 | - | + (c) | - | - | - | 8 | 0.5 | <0.25 | 32 | 4 | 0.125 |
E. faecium Z0219EM0049 | May 2019, Gyeongsang | Chicken | Skin | 446 | - | + (c) | - | - | - | 8 | 1 | <0.25 | 64 | 4 | 0.125 |
E. faecium Z0219EM0050 | May 2019, Gyeongsang | Chicken | Skin | 446 | - | + (c) | - | - | - | 8 | 1 | 0.5 | 64 | 4 | 0.125 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
On, Y.; Lee, S.Y.; Yoo, J.S.; Kim, J.W. Molecular Epidemiology and Genetic Context of optrA-Carrying Linezolid-Resistant Enterococci from Humans and Animals in South Korea. Antibiotics 2025, 14, 571. https://doi.org/10.3390/antibiotics14060571
On Y, Lee SY, Yoo JS, Kim JW. Molecular Epidemiology and Genetic Context of optrA-Carrying Linezolid-Resistant Enterococci from Humans and Animals in South Korea. Antibiotics. 2025; 14(6):571. https://doi.org/10.3390/antibiotics14060571
Chicago/Turabian StyleOn, Younggwon, Sung Young Lee, Jung Sik Yoo, and Jung Wook Kim. 2025. "Molecular Epidemiology and Genetic Context of optrA-Carrying Linezolid-Resistant Enterococci from Humans and Animals in South Korea" Antibiotics 14, no. 6: 571. https://doi.org/10.3390/antibiotics14060571
APA StyleOn, Y., Lee, S. Y., Yoo, J. S., & Kim, J. W. (2025). Molecular Epidemiology and Genetic Context of optrA-Carrying Linezolid-Resistant Enterococci from Humans and Animals in South Korea. Antibiotics, 14(6), 571. https://doi.org/10.3390/antibiotics14060571