Skip to content
1887

Abstract

Mobile linezolid-resistance genes (, and ) that confer resistance to linezolid and florfenicol have been detected globally in various sources. Linezolid is a last-resort antimicrobial used in human clinical settings, and florfenicol is commonly used in veterinary clinical settings. The present study sought to evaluate the potential of florfenicol in veterinary use to select for linezolid-resistant bacteria. The growth and fitness of linezolid-resistant bacteria harbouring mobile linezolid-resistance genes were assessed in the presence and absence of florfenicol using and , respectively. The bacterial strains harboured wild and cloning plasmids carrying mobile linezolid-resistance genes, which reduced their susceptibility to linezolid and florfenicol. The acquisition of plasmids carrying mobile linezolid-resistance genes improved bacterial growth in the presence of florfenicol and conferred fitness costs in its absence. Florfenicol imposes a selection pressure on bacteria harbouring plasmids carrying mobile linezolid-resistance genes. Hence, the appropriate use of florfenicol in veterinary clinical settings is important to control the dissemination of mobile linezolid-resistance genes and to ensure the sustained effectiveness of linezolid against multidrug-resistant bacteria, including vancomycin-resistant enterococci in human clinical settings.

Funding
This study was supported by the:
  • JSPS KAKENHI (Award 23K17049)
    • Principle Award Recipient: AkiraFukuda
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/acmi/10.1099/acmi.0.000997.v3
2025-04-08
2025-04-21
Loading full text...

Full text loading...

/deliver/fulltext/acmi/7/4/acmi000997.v3.html?itemId=/content/journal/acmi/10.1099/acmi.0.000997.v3&mimeType=html&fmt=ahah

References

  1. Woolhouse M, Ward M, van Bunnik B, Farrar J. Antimicrobial resistance in humans, livestock and the wider environment. Phil Trans R Soc B 2015; 370:20140083 [View Article]
    [Google Scholar]
  2. Bender JK, Cattoir V, Hegstad K, Sadowy E, Coque TM 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 [View Article] [PubMed]
    [Google Scholar]
  3. Schwarz S, Zhang W, Du X-D, Krüger H, Feßler AT et al. Mobile oxazolidinone resistance genes in gram-positive and gram-negative bacteria. Clin Microbiol Rev 2021; 34:e0018820 [View Article] [PubMed]
    [Google Scholar]
  4. Brenciani A, Morroni G, Schwarz S, Giovanetti E. Oxazolidinones: mechanisms of resistance and mobile genetic elements involved. J Antimicrob Chemother 2022; 77:2596–2621 [View Article] [PubMed]
    [Google Scholar]
  5. Fukuda A, Nakajima C, Suzuki Y, Usui M. Transferable linezolid resistance genes (optrA and poxtA) in enterococci derived from livestock compost at Japanese farms. J Glob Antimicrob Resist 2024; 36:336–344 [View Article] [PubMed]
    [Google Scholar]
  6. Liu Z, Zhao Q, Xu C, Song H. Compensatory evolution of chromosomes and plasmids counteracts the plasmid fitness cost. Ecol Evol 2024; 14:e70121 [View Article] [PubMed]
    [Google Scholar]
  7. Long KS, Vester B. Resistance to linezolid caused by modifications at its binding site on the ribosome. Antimicrob Agents Chemother 2012; 56:603–612 [View Article] [PubMed]
    [Google Scholar]
  8. Guo X, Chen H, Tong Y, Wu X, Tang C et al. A review on the antibiotic florfenicol: occurrence, environmental fate, effects, and health risks. Environ Res 2024; 244:117934 [View Article]
    [Google Scholar]
  9. Wang Y, Li X, Fu Y, Chen Y, Wang Y et al. Association of florfenicol residues with the abundance of oxazolidinone resistance genes in livestock manures. J Hazard Mater 2020; 399:123059 [View Article]
    [Google Scholar]
  10. Turner AM, Lee JYH, Gorrie CL, Howden BP, Carter GP. Genomic insights into last-line antimicrobial resistance in multidrug-resistant Staphylococcus and vancomycin-resistant Enterococcus. Front Microbiol 2021; 12:637656 [View Article] [PubMed]
    [Google Scholar]
  11. Zhang E, Zong S, Zhou W, Zhou J, Han J et al. Characterization and comparative genomics analysis of RepA_N multi-resistance plasmids carrying optrA from Enterococcus faecalis. Front Microbiol 2022; 13:991352 [View Article] [PubMed]
    [Google Scholar]
  12. Shan X, Li C, Zhang L, Zou C, Yu R et al. poxtA amplification and mutations in 23S rRNA confer enhanced linezolid resistance in Enterococcus faecalis. J Antimicrob Chemother 2024; 79:3199–3203 [View Article] [PubMed]
    [Google Scholar]
  13. Wang Y, Lv Y, Cai J, Schwarz S, Cui L 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 [View Article] [PubMed]
    [Google Scholar]
  14. Antonelli A, D’Andrea MM, Brenciani A, Galeotti CL, Morroni G et al. Characterization of poxtA, a novel phenicol-oxazolidinone-tetracycline resistance gene from an MRSA of clinical origin. J Antimicrob Chemother 2018; 73:1763–1769 [View Article] [PubMed]
    [Google Scholar]
  15. Long KS, 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 [View Article] [PubMed]
    [Google Scholar]
  16. Sato T. Studies on molecular epidemiology of methicillinresistant staphylococcus aureus originated from livestock animals, meat products, and humans. Rakuno gakuen university 2018
    [Google Scholar]
  17. Nickoloff JA. Electroporation protocols for microorganisms. Methods Mol Biol 19951–372 [View Article]
    [Google Scholar]
  18. Clinical and Laboratory Standard Institute Performance standards for antimicrobial susceptibility testing, M100 34th edn. Wayne, PA: CLSI;
  19. Chen Z, Xiong Y, Tang Y, Zhao Y, Chen J et al. In vitro activities of thiazolidione derivatives combined with daptomycin against clinical Enterococcus faecium strains. BMC Microbiol 2022; 22:16 [View Article] [PubMed]
    [Google Scholar]
  20. Liu Z, Zhang H, Xiao X, Liu Y, Li R et al. Comparison of fitness cost, stability, and conjugation frequencies of tet(X4)-positive plasmids in chicken and pig Escherichia coli. Antibiotics 2022; 11:1657 [View Article] [PubMed]
    [Google Scholar]
  21. Starikova I, Al-Haroni M, Werner G, Roberts AP, Sørum V et al. Fitness costs of various mobile genetic elements in Enterococcus faecium and Enterococcus faecalis. J Antimicrob Chemother 2013; 68:2755–2765 [View Article] [PubMed]
    [Google Scholar]
  22. Shen W, Cai C, Dong N, Chen J, Zhang R et al. Mapping the widespread distribution and transmission dynamics of linezolid resistance in humans, animals, and the environment. Microbiome 2024; 12:52 [View Article] [PubMed]
    [Google Scholar]
  23. Gawryszewska I, Żabicka D, Hryniewicz W, Sadowy E. Linezolid-resistant enterococci in Polish hospitals: species, clonality and determinants of linezolid resistance. Eur J Clin Microbiol Infect Dis 2017; 36:1279–1286 [View Article] [PubMed]
    [Google Scholar]
  24. Fujiya Y, Harada T, Sugawara Y, Akeda Y, Yasuda M et al. Transmission dynamics of a linear vanA-plasmid during a nosocomial multiclonal outbreak of vancomycin-resistant enterococci in a non-endemic area, Japan. Sci Rep 2021; 11:14780 [View Article] [PubMed]
    [Google Scholar]
  25. Dorado-Morales P, Garcillán-Barcia MP, Lasa I, Solano C. Fitness cost evolution of natural plasmids of Staphylococcus aureus. mBio 2021; 12:1–18 [View Article] [PubMed]
    [Google Scholar]
  26. Hashimoto Y, Suzuki M, Kobayashi S, Hirahara Y, Kurushima J et al. Enterococcal linear plasmids adapt to Enterococcus faecium and spread within multidrug-resistant clades. Antimicrob Agents Chemother 2023; 67:e0161922 [View Article] [PubMed]
    [Google Scholar]
  27. Lee T, Pang S, Abraham S, Coombs GW. Antimicrobial-resistant CC17 Enterococcus faecium: the past, the present and the future. J Glob Antimicrob Resist 2019; 16:36–47 [View Article] [PubMed]
    [Google Scholar]
  28. Lee JB, Lim JH, Park JH, Lee GY, Park KT et al. Genetic characteristics and antimicrobial resistance of Staphylococcus aureus isolates from pig farms in Korea: emergence of cfr-positive CC398 lineage. BMC Vet Res 2024; 20:503 [View Article] [PubMed]
    [Google Scholar]
/content/journal/acmi/10.1099/acmi.0.000997.v3
Loading
/content/journal/acmi/10.1099/acmi.0.000997.v3
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error