1887

Microbial Genomics logo

Volume 9, Issue 5

Genomic surveillance of multidrug-resistant in Wales reveals persistent spread of ST307 and adaptive evolution of pOXA-48-like plasmids Open Access

Abstract

Rising rates of multidrug-resistant infections necessitate a comprehensive understanding of the major strains and plasmids driving spread of resistance elements. Here, we analysed 540 clinical, screen and environmental isolates recovered from across Wales between 2007 and 2020 using combined short- and long-read sequencing approaches. We identified resistant clones that have spread within and between hospitals including the high-risk strain sequence type (ST)307, which acquired the carbapenemase gene on a pOXA-48-like plasmid. We found evidence that this strain, which caused an acute outbreak largely centred on a single hospital in 2019, had been circulating undetected across South Wales for several years prior to the outbreak. In addition to clonal transmission, our analyses revealed evidence for substantial plasmid spread, mostly notably involving and (including ) carbapenemase genes that were found among many species and strain backgrounds. Two thirds (20/30) of the genes were carried on the Tn transposon and associated with IncF plasmids. These were mostly recovered from patients in North Wales, reflecting an outward expansion of the plasmid-driven outbreak of -producing in North-West England. A total of 92.1 % (105/114) of isolates with a carbapenemase carried the gene on a pOXA-48-like plasmid. While this plasmid family is highly conserved, our analyses revealed novel accessory variation including integrations of additional resistance genes. We also identified multiple independent deletions involving the gene cluster among pOXA-48-like plasmids in the ST307 outbreak lineage. These resulted in loss of conjugative ability and signal adaptation of the plasmids to carriage by the host strain. Altogether, our study provides, to our knowledge, the first high resolution view of the diversity, transmission and evolutionary dynamics of major resistant clones and plasmids of in Wales, and forms an important basis for ongoing surveillance efforts. This article contains data hosted by Microreact.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): genomic surveillance , carbapenem resistance , carbapenemase , Klebsiella , pOXA-48-like plasmids and ST307
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution 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/mgen/10.1099/mgen.0.001016
2023-05-25
2024-05-06
Loading full text...

Full text loading...

/deliver/fulltext/mgen/9/5/mgen001016.html?itemId=/content/journal/mgen/10.1099/mgen.0.001016&mimeType=html&fmt=ahah

References

  1. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014; 370:1198–1208 [View Article] [PubMed]
     [Google Scholar]
  2. Ling ML, Apisarnthanarak A, Madriaga G. The burden of healthcare-associated infections in Southeast Asia: a systematic literature review and meta-analysis. Clin Infect Dis 2015; 60:1690–1699 [View Article] [PubMed]
     [Google Scholar]
  3. Vincent J-L, Sakr Y, Singer M, Martin-Loeches I, Machado FR et al. Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA 2020; 323:1478–1487 [View Article] [PubMed]
     [Google Scholar]
  4. Meatherall BL, Gregson D, Ross T, Pitout JDD, Laupland KB. Incidence, risk factors, and outcomes of Klebsiella pneumoniae bacteremia. Am J Med 2009; 122:866–873 [View Article] [PubMed]
     [Google Scholar]
  5. Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 1998; 11:589–603 [View Article] [PubMed]
     [Google Scholar]
  6. Gorrie CL, Mirceta M, Wick RR, Edwards DJ, Thomson NR et al. Gastrointestinal carriage is a major reservoir of Klebsiella pneumoniae infection in intensive care patients. Clin Infect Dis 2017; 65:208–215 [View Article] [PubMed]
     [Google Scholar]
  7. Snitkin ES, Zelazny AM, Thomas PJ, Stock F et al.NISC Comparative Sequencing Program Group Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Sci Transl Med 2012; 4:148ra116 [View Article] [PubMed]
     [Google Scholar]
  8. Gu D, Dong N, Zheng Z, Lin D, Huang M et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis 2018; 18:37–46 [View Article] [PubMed]
     [Google Scholar]
  9. Tavoschi L, Forni S, Porretta A, Righi L, Pieralli F et al. Prolonged outbreak of New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE), Tuscany, Italy, 2018 to 2019. Euro Surveill 2020; 25:2000085 [View Article] [PubMed]
     [Google Scholar]
  10. Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A et al. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis 2019; 19:56–66 [View Article] [PubMed]
     [Google Scholar]
  11. Castanheira M, Deshpande LM, Mendes RE, Canton R, Sader HS et al. Variations in the occurrence of resistance phenotypes and carbapenemase genes among Enterobacteriaceae isolates in 20 years of the SENTRY antimicrobial surveillance program. Open Forum Infect Dis 2019; 6:S23–S33 [View Article] [PubMed]
     [Google Scholar]
  12. WHO Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics Geneva: World Health Organization; 2017
     [Google Scholar]
  13. Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 2007; 20:440–458 [View Article] [PubMed]
     [Google Scholar]
  14. Bradley N, Lee Y. Practical implications of new antibiotic agents for the treatment of carbapenem-resistant enterobacteriaceae. Microbiol Insights 2019; 12:1178636119840367 [View Article] [PubMed]
     [Google Scholar]
  15. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012; 19:455–477 [View Article] [PubMed]
     [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. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
     [Google Scholar]
  18. Lam MMC, Wick RR, Watts SC, Cerdeira LT, Wyres KL et al. A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex. Nat Commun 2021; 12:4188 [View Article] [PubMed]
     [Google Scholar]
  19. Wyres KL, Wick RR, Gorrie C, Jenney A, Follador R et al. Identification of Klebsiella capsule synthesis loci from whole genome data. Microb Genom 2016; 2:e000102 [View Article] [PubMed]
     [Google Scholar]
  20. Tonkin-Hill G, MacAlasdair N, Ruis C, Weimann A, Horesh G et al. Producing polished prokaryotic pangenomes with the Panaroo pipeline. Genome Biol 2020; 21:180 [View Article] [PubMed]
     [Google Scholar]
  21. Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom 2016; 2:000056 [View Article]
     [Google Scholar]
  22. Nguyen L-T, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 2015; 32:268–274 [View Article] [PubMed]
     [Google Scholar]
  23. Argimón S, David S, Underwood A, Abrudan M, Wheeler NE et al. Rapid genomic characterization and global surveillance of Klebsiella using pathogenwatch. Clin Infect Dis 2021; 73:S325–S335 [View Article] [PubMed]
     [Google Scholar]
  24. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25:1754–1760 [View Article] [PubMed]
     [Google Scholar]
  25. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009; 25:2078–2079 [View Article] [PubMed]
     [Google Scholar]
  26. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015; 43:e15 [View Article] [PubMed]
     [Google Scholar]
  27. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 2021; 49:W293–W296 [View Article] [PubMed]
     [Google Scholar]
  28. Argimón S, Abudahab K, Goater RJE, Fedosejev A, Bhai J et al. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microb Genom 2016; 2:e000093 [View Article] [PubMed]
     [Google Scholar]
  29. Carattoli A, Zankari E, García-Fernández 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] [PubMed]
     [Google Scholar]
  30. Li X, Xie Y, Liu M, Tai C, Sun J et al. oriTfinder: a web-based tool for the identification of origin of transfers in DNA sequences of bacterial mobile genetic elements. Nucleic Acids Res 2018; 46:W229–W234 [View Article] [PubMed]
     [Google Scholar]
  31. Sullivan MJ, Petty NK, Beatson SA. Easyfig: a genome comparison visualizer. Bioinformatics 2011; 27:1009–1010 [View Article] [PubMed]
     [Google Scholar]
  32. 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]
  33. Kurtz S, Phillippy A, Delcher AL, Smoot M, Shumway M et al. Versatile and open software for comparing large genomes. Genome Biol 2004; 5:R12 [View Article] [PubMed]
     [Google Scholar]
  34. Sheppard AE, Stoesser N, German-Mesner I, Vegesana K, Walker AS et al. TETyper: a bioinformatic pipeline for classifying variation and genetic contexts of transposable elements from short-read whole-genome sequencing data. Microb Genom 2018; 4:000232 [View Article] [PubMed]
     [Google Scholar]
  35. Poirel L, Bonnin RA, Nordmann P. Genetic features of the widespread plasmid coding for the carbapenemase OXA-48. Antimicrob Agents Chemother 2012; 56:559–562 [View Article] [PubMed]
     [Google Scholar]
  36. Zhou Z, Alikhan N-F, Sergeant MJ, Luhmann N, Vaz C et al. GrapeTree: visualization of core genomic relationships among 100,000 bacterial pathogens. Genome Res 2018; 28:1395–1404 [View Article] [PubMed]
     [Google Scholar]
  37. Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 2010; 26:841–842 [View Article] [PubMed]
     [Google Scholar]
  38. Peirano G, Chen L, Kreiswirth BN, Pitout JDD. Emerging antimicrobial-resistant high-risk Klebsiella pneumoniae clones ST307 and ST147. Antimicrob Agents Chemother 2020; 64:10 [View Article] [PubMed]
     [Google Scholar]
  39. Martínez-Martínez L, Pascual A, Hernández-Allés S, Alvarez-Díaz D, Suárez AI et al. Roles of beta-lactamases and porins in activities of carbapenems and cephalosporins against Klebsiella pneumoniae. Antimicrob Agents Chemother 1999; 43:1669–1673 [View Article] [PubMed]
     [Google Scholar]
  40. Hamzaoui Z, Ocampo-Sosa A, Maamar E, Fernandez Martinez M, Ferjani S et al. An outbreak of NDM-1-producing Klebsiella pneumoniae, associated with OmpK35 and OmpK36 porin loss in Tunisia. Microb Drug Resist 2018; 24:1137–1147 [View Article] [PubMed]
     [Google Scholar]
  41. Shon AS, Bajwa RPS, Russo TA. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence 2013; 4:107–118 [View Article] [PubMed]
     [Google Scholar]
  42. Babiker A, Bower C, Lutgring JD, Petit RA, Howard-Anderson J et al. Clinical and genomic epidemiology of mcr-9-carrying carbapenem-resistant enterobacterales isolates in Metropolitan Atlanta, 2012 to 2017. Microbiol Spectr 2022; 10:e0252221 [View Article] [PubMed]
     [Google Scholar]
  43. Kieffer N, Royer G, Decousser J-W, Bourrel A-S, Palmieri M et al. mcr-9, an inducible gene encoding an acquired phosphoethanolamine transferase in Escherichia coli, and its origin. Antimicrob Agents Chemother 2019; 63:e00965-19 [View Article] [PubMed]
     [Google Scholar]
  44. Naas T, Cuzon G, Villegas MV, Lartigue MF, Quinn JP et al. Genetic structures at the origin of acquisition of the beta-lactamase blaKPC gene. Antimicrob Agents Chemother 2008; 52:1257–1263 [View Article] [PubMed]
     [Google Scholar]
  45. Cuzon G, Naas T, Nordmann P. Functional characterization of Tn4401, a Tn3-based transposon involved in blaKPC gene mobilization. Antimicrob Agents Chemother 2011; 55:5370–5373 [View Article] [PubMed]
     [Google Scholar]
  46. Stoesser N, Phan HTT, Seale AC, Aiken Z, Thomas S et al. Genomic epidemiology of complex, multi-species, plasmid-borne blaKPC carbapenemase in Enterobacterales in the United Kingdom from 2009 to 2014. Antimicrob Agents Chemother 2020; 64:e02244-19 [PubMed]
     [Google Scholar]
  47. Leavitt A, Chmelnitsky I, Carmeli Y, Navon-Venezia S. Complete nucleotide sequence of KPC-3-encoding plasmid pKpQIL in the epidemic Klebsiella pneumoniae sequence type 258. Antimicrob Agents Chemother 2010; 54:4493–4496 [View Article] [PubMed]
     [Google Scholar]
  48. Villa L, Feudi C, Fortini D, Brisse S, Passet V et al. Diversity, virulence, and antimicrobial resistance of the KPC-producing Klebsiella pneumoniae ST307 clone. Microb Genom 2017; 3:e000110 [View Article] [PubMed]
     [Google Scholar]
  49. David S, Cohen V, Reuter S, Sheppard AE, Giani T et al. Integrated chromosomal and plasmid sequence analyses reveal diverse modes of carbapenemase gene spread among Klebsiella pneumoniae. Proc Natl Acad Sci 2020; 117:25043–25054 [View Article] [PubMed]
     [Google Scholar]
  50. Carattoli A, Seiffert SN, Schwendener S, Perreten V, Endimiani A. Differentiation of IncL and IncM plasmids associated with the spread of clinically relevant antimicrobial resistance. PLoS One 2015; 10:e0123063 [View Article] [PubMed]
     [Google Scholar]
  51. Public Health Wales Antibacterial Resistance in Wales 2008–2017 Cardiff: Public Health Wales; 2018
     [Google Scholar]
  52. David S, Reuter S, Harris SR, Glasner C, Feltwell T et al. Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread. Nat Microbiol 2019; 4:1919–1929 [View Article] [PubMed]
     [Google Scholar]
  53. Bonnin RA, Jousset AB, Chiarelli A, Emeraud C, Glaser P et al. Emergence of new non-clonal group 258 high-risk clones among Klebsiella pneumoniae carbapenemase-producing K. pneumoniae isolates, France. Emerg Infect Dis 2020; 26:1212–1220 [View Article] [PubMed]
     [Google Scholar]
  54. Di Pilato V, Errico G, Monaco M, Giani T, Del Grosso M et al. The changing epidemiology of carbapenemase-producing Klebsiella pneumoniae in Italy: toward polyclonal evolution with emergence of high-risk lineages. J Antimicrob Chemother 2021; 76:355–361 [View Article] [PubMed]
     [Google Scholar]
  55. Lowe M, Kock MM, Coetzee J, Hoosien E, Peirano G et al. Klebsiella pneumoniae ST307 with blaOXA-181, South Africa, 2014-2016. Emerg Infect Dis 2019; 25:739–747 [View Article] [PubMed]
     [Google Scholar]
  56. Haller S, Kramer R, Becker K, Bohnert JA, Eckmanns T et al. Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019. Euro Surveill 2019; 24:1900734 [View Article] [PubMed]
     [Google Scholar]
  57. Skalova A, Chudejova K, Rotova V, Medvecky M, Studentova V et al. Molecular characterization of OXA-48-like-producing enterobacteriaceae in the Czech Republic and evidence for horizontal transfer of pOXA-48-like plasmids. Antimicrob Agents Chemother 2017; 61:e01889-16 [View Article] [PubMed]
     [Google Scholar]
  58. Brehony C, McGrath E, Brennan W, Tuohy A, Whyte T et al. An MLST approach to support tracking of plasmids carrying OXA-48-like carbapenemase. J Antimicrob Chemother 2019; 74:1856–1862 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.001016
Loading
Genomic surveillance of multidrug-resistant Klebsiella in Wales reveals persistent spread of Klebsiella pneumoniae ST307 and adaptive evolution of pOXA-48-like plasmids
M Gen 9, 001016 (2023); https://doi.org/10.1099/mgen.0.001016
/content/journal/mgen/10.1099/mgen.0.001016
/content/journal/mgen/10.1099/mgen.0.001016
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL

Supplementary material 2

EXCEL

Supplementary material 3

PDF

Supplementary material 4

EXCEL

Most cited Most Cited RSS feed

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