1887

Abstract

. The New Delhi metallo-β-lactamase (NDM) variant NDM-5 was first described in 2011 in an isolate of . We noted that a high proportion of isolates of positive for carbapenemase genes submitted to the UK Health Security Agency (formerly Public Health England) between 2019 and mid-2021 carried the allele, with many co-harbouring , rendering them highly resistant to aminoglycosides as well as to most β-lactams.

. This observation suggested that a common plasmid may be circulating.

. To compare these isolates and describe the plasmids carrying these resistance elements.

. All isolates were sequenced on an Illumina platform, with five also subjected to long-read nanopore sequencing to provide complete assemblies. The locations of , and other associated genetic elements were identified. Susceptibility testing to a wide range of antibiotics was carried out on representative isolates.

. The 34 isolates co-harbouring and were from 14 hospital groups and six different regions across England and consisted of 11 distinct sequence types. All carried IncF plasmids. Assembly of the NDM plasmids in five isolates revealed that they carried and in an IncF conjugative plasmid ranging in size from 85.5 to 161 kb. All carried a highly conserved region, previously described in plasmid pHC105-NDM, that included and followed by sequence bounded by two IS elements containing ΔIS, , , and followed by IS and an integron with , and cassettes. This arrangement has been described in isolates from other countries and continents, suggesting that such plasmids are widely distributed, at least in , with similar plasmids also found in . Tested isolates were resistant to most antibiotics except colistin, fosfomycin and tigecycline.

. These observations suggest that conjugative plasmids carrying a highly conserved resistance gene segment have become widespread in England and elsewhere. This study highlights the value of routine whole-genome sequencing in identifying genetic elements responsible for resistance dissemination.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001569
2022-08-04
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jmm/71/8/jmm001569.html?itemId=/content/journal/jmm/10.1099/jmm.0.001569&mimeType=html&fmt=ahah

References

  1. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009; 53:5046–5054 [View Article] [PubMed]
    [Google Scholar]
  2. Hornsey M, Phee L, Wareham DW. A novel variant, NDM-5, of the New Delhi metallo-β-lactamase in a multidrug-resistant Escherichia coli ST648 isolate recovered from a patient in the United Kingdom. Antimicrob Agents Chemother 2011; 55:5952–5954 [View Article] [PubMed]
    [Google Scholar]
  3. Taylor E, Sriskandan S, Woodford N, Hopkins KL. High prevalence of 16S rRNA methyltransferases among carbapenemase-producing Enterobacteriaceae in the UK and Ireland. Int J Antimicrob Agents 2018; 52:278–282 [View Article] [PubMed]
    [Google Scholar]
  4. Taylor E, Bal AM, Balakrishnan I, Brown NM, Burns P et al. A prospective surveillance study to determine the prevalence of 16S rRNA methyltransferase-producing Gram-negative bacteria in the UK. J Antimicrob Chemother 2021; 76:2428–2436 [View Article] [PubMed]
    [Google Scholar]
  5. Wu W, Feng Y, Tang G, Qiao F, McNally A et al. NDM metallo-β-lactamases and their bacterial producers in health care settings. Clin Microbiol Rev 2019; 32:e00115-18 [View Article] [PubMed]
    [Google Scholar]
  6. Costa A, Figueroa-Espinosa R, Gaudenzi F, Lincopan N, Fuga B et al. Co-occurrence of NDM-5 and RmtB in a clinical isolate of Escherichia coli belonging to CC354 in Latin America. Front Cell Infect Microbiol 2021; 11:654852 [View Article] [PubMed]
    [Google Scholar]
  7. Pitart C, Solé M, Roca I, Román A, Moreno A et al. Molecular characterization of blaNDM-5 carried on an IncFII plasmid in an Escherichia coli isolate from a nontraveler patient in Spain. Antimicrob Agents Chemother 2015; 59:659–662 [View Article] [PubMed]
    [Google Scholar]
  8. Zhu Y-Q, Zhao J-Y, Xu C, Zhao H, Jia N et al. Identification of an NDM-5-producing Escherichia coli sequence type 167 in a neonatal patient in China. Sci Rep 2016; 6:29934 [View Article] [PubMed]
    [Google Scholar]
  9. Devanga Ragupathi NK, Veeraraghavan B, Muthuirulandi Sethuvel DP, Anandan S, Vasudevan K et al. First Indian report on genome-wide comparison of multidrug-resistant Escherichia coli from blood stream infections. PLoS One 2020; 15:e0220428 [View Article] [PubMed]
    [Google Scholar]
  10. Chudejova K, Kraftova L, Mattioni Marchetti V, Hrabak J, Papagiannitsis CC et al. Genetic plurality of OXA/NDM-encoding features characterized from Enterobacterales recovered from Czech Hospitals. Front Microbiol 2021; 12:641415 [View Article] [PubMed]
    [Google Scholar]
  11. Chakraborty T, Sadek M, Yao Y, Imirzalioglu C, Stephan R et al. Cross-border emergence of Escherichia coli producing the carbapenemase NDM-5 in Switzerland and Germany. J Clin Microbiol 2021; 59:e02238-20 [View Article] [PubMed]
    [Google Scholar]
  12. Shin J, Baek JY, Cho SY, Huh HJ, Lee NY et al. blaNDM-5-bearing IncFII-type plasmids of Klebsiella pneumoniae sequence type 147 transmitted by cross-border transfer of a patient. Antimicrob Agents Chemother 2016; 60:1932–1934 [View Article] [PubMed]
    [Google Scholar]
  13. Dallman T, Ashton P, Schafer U, Jironkin A, Painset A et al. SnapperDB: a database solution for routine sequencing analysis of bacterial isolates. Bioinformatics 2018; 34:3028–3029 [View Article] [PubMed]
    [Google Scholar]
  14. Doumith M, Godbole G, Ashton P, Larkin L, Dallman T et al. Detection of the plasmid-mediated mcr-1 gene conferring colistin resistance in human and food isolates of Salmonella enterica and Escherichia coli in England and Wales. J Antimicrob Chemother 2016; 71:2300–2305 [View Article] [PubMed]
    [Google Scholar]
  15. Wang J, Bleich RM, Zarmer S, Zhang S, Dogan B et al. Long-read sequencing to interrogate strain-level variation among adherent-invasive Escherichia coli isolated from human intestinal tissue. PLoS One 2021; 16:e0259141 [View Article]
    [Google Scholar]
  16. Wick RR, Judd LM, Gorrie CL, Holt KE. Unicycler: resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput Biol 2017; 13:e1005595 [View Article] [PubMed]
    [Google Scholar]
  17. Bortolaia V, Kaas RS, Ruppe E, Roberts MC, Schwarz S et al. ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother 2020; 75:3491–3500 [View Article] [PubMed]
    [Google Scholar]
  18. Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J et al. BLAST+: architecture and applications. BMC Bioinformatics 2009; 10:421 [View Article] [PubMed]
    [Google Scholar]
  19. Carattoli A, Zankari E, Garcia-Fernandez A, Voldby Larsen M, Lund O et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 2014; 58:3895–3903 [View Article]
    [Google Scholar]
  20. Veltri D, Wight MM, Crouch JA. SimpleSynteny: a web-based tool for visualization of microsynteny across multiple species. Nucleic Acids Res 2016; 44:W41–W45 [View Article] [PubMed]
    [Google Scholar]
  21. Gilchrist CLM, Chooi Y-H. Clinker & clustermap.js: automatic generation of gene cluster comparison figures. Bioinformatics 2021; 37:2473–2475 [View Article] [PubMed]
    [Google Scholar]
  22. Doern CD. When does 2 plus 2 equal 5? A review of antimicrobial synergy testing. J Clin Microbiol 2014; 52:4124–4128 [View Article] [PubMed]
    [Google Scholar]
  23. Sugawara Y, Akeda Y, Hagiya H, Sakamoto N, Takeuchi D et al. Spreading patterns of NDM-producing Enterobacteriaceae in clinical and environmental settings in Yangon, Myanmar. Antimicrob Agents Chemother 2019; 63:e01924-18 [View Article] [PubMed]
    [Google Scholar]
  24. Hopkins KL, Ellaby N, Ellington MJ, Doumith M, Mustafa N et al. Diversity of carbapenemase-producing Enterobacterales in England as revealed by whole-genome sequencing of isolates referred to a national reference laboratory over a 30-month period. J Med Microbiol 2022; 71:e001518 [View Article] [PubMed]
    [Google Scholar]
  25. Davido B, Fellous L, Lawrence C, Maxime V, Rottman M et al. Ceftazidime-avibactam and aztreonam, an interesting strategy to overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother 2017; 61:e01008-17 [View Article] [PubMed]
    [Google Scholar]
  26. Sadek M, Ruppé E, Habib A, Zahra R, Poirel L et al. International circulation of aztreonam/avibactam-resistant NDM-5-producing Escherichia coli isolates: successful epidemic clones. J Glob Antimicrob Resist 2021; 27:326–328 [View Article] [PubMed]
    [Google Scholar]
  27. Alm RA, Johnstone MR, Lahiri SD. Characterization of Escherichia coli NDM isolates with decreased susceptibility to aztreonam/avibactam: role of a novel insertion in PBP3. J Antimicrob Chemother 2015; 70:1420–1428 [View Article] [PubMed]
    [Google Scholar]
  28. Wachino JI, Doi Y, Arakawa Y. Aminoglycoside resistance: updates with a focus on acquired 16S ribosomal RNA methyltransferases. Infect Dis Clin North Am 2020; 34:887–902 [View Article] [PubMed]
    [Google Scholar]
  29. Virulence factors of pathogenic bacteria: Escherichia. Beijing: NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, CAMS and PUMC; 2022 http://www.mgc.ac.cn/cgi-bin/VFs/genus.cgi?Genus=Escherichia
  30. Graf FE, Palm M, Warringer J, Farewell A. Inhibiting conjugation as a tool in the fight against antibiotic resistance. Drug Dev Res 2019; 80:19–23 [View Article] [PubMed]
    [Google Scholar]
  31. Nadar S, Khan T, Patching SG, Omri A. Development of antibiofilm therapeutics strategies to overcome antimicrobial drug resistance. Microorganisms 2022; 10:303 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001569
Loading
/content/journal/jmm/10.1099/jmm.0.001569
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