1887

Abstract

is a concern because of its multidrug resistance and the ability of hypervirulent types, especially capsular type K1-clonal complex 23 (K1-CC23), to cause community-acquired, life-threatening infections. Hypervirulent types carry an array of virulence genes including /, coding for capsule up-regulation. We sought to identify isolates carrying these elements among submissions to the UK national reference laboratory during 2016.

Virulence elements and carbapenemase genes were sought by PCR or from whole genome sequences. Isolates were typed by variable number tandem repeat analysis or by multi locus sequence typing from whole genome sequences. Long read nanopore sequencing was carried out on two isolates.

Twelve of 1090 isolates (1.1 %) belonged to hypervirulent K1-CC23, with one carrying (KpvST23L_OXA-48). A further 24 /-positive isolates were detected: eight belonged to hypervirulent types of capsular types K2 and K54; and 14 belonged to ‘non-hypervirulent’ ST147, ST15 and ST383 and also carried carbapenemase gene(s). Virulence, heavy metal and antibiotic resistance gene contents were compared from whole genome sequences of KpvST23L_OXA-48 and one of the ST147 isolates carrying . They carried 94/96 and 26/96 of the virulence genes sought, and 23/23 and 9/23 of the heavy metal resistance genes, respectively. In the ST147 isolate, / and the aerobactin siderophore cluster were on a large virulence plasmid together with resistance genes. The yersiniabactin cluster was widely present among carbapenemase gene-positive isolates, including among those that were /negative.

Our results highlight a combination of virulence and resistance genes, which could lead to untreatable invasive infections.

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2018-01-01
2024-03-28
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References

  1. Shon AS, Bajwa RP, Russo TA. Hypervirulent (hypermucoviscous) Klebsiella pneumoniae: a new and dangerous breed. Virulence 2013; 4:107–118 [View Article][PubMed]
    [Google Scholar]
  2. Chen YT, Chang HY, Lai YC, Pan CC, Tsai SF et al. Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43. Gene 2004; 337:189–198 [View Article][PubMed]
    [Google Scholar]
  3. Wu KM, Li LH, Yan JJ, Tsao N, Liao TL et al. Genome sequencing and comparative analysis of Klebsiella pneumoniae NTUH-K2044, a strain causing liver abscess and meningitis. J Bacteriol 2009; 191:4492–4501 [View Article][PubMed]
    [Google Scholar]
  4. Li W, Sun G, Yu Y, Li N, Chen M et al. Increasing occurrence of antimicrobial-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae isolates in China. Clin Infect Dis 2014; 58:225–232 [View Article][PubMed]
    [Google Scholar]
  5. Cejas D, Fernández Canigia L, Rincón Cruz G, Elena AX, Maldonado I et al. First isolate of KPC-2-producing Klebsiella pneumonaie sequence type 23 from the Americas. J Clin Microbiol 2014; 52:3483–3485 [View Article][PubMed]
    [Google Scholar]
  6. Zhang R, Lin D, Chan EW, Gu D, Chen GX et al. Emergence of carbapenem-resistant serotype K1 hypervirulent Klebsiella pneumoniae strains in China. Antimicrob Agents Chemother 2015; 60:709–711 [View Article][PubMed]
    [Google Scholar]
  7. Roulston KJ, Bharucha T, Turton JF, Hopkins KL, Mack D. A case of NDM-carbapenemase producing hypervirulent Klebsiella pneumoniae Sequence Type 23 from the United Kingdom. JMM Case Rep (in pres)
    [Google Scholar]
  8. Holt KE, Wertheim H, Zadoks RN, Baker S, Whitehouse CA et al. Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proc Natl Acad Sci USA 2015; 112:E3574E3581 [View Article][PubMed]
    [Google Scholar]
  9. Paczosa MK, Mecsas J. Klebsiella pneumoniae: going on the offense with a strong defense. Microbiol Mol Biol Rev 2016; 80:629–661 [View Article][PubMed]
    [Google Scholar]
  10. Passet V, Brisse S. Association of tellurite resistance with hypervirulent clonal groups of Klebsiella pneumoniae . J Clin Microbiol 2015; 53:1380–1382 [View Article][PubMed]
    [Google Scholar]
  11. Ye M, Tu J, Jiang J, Bi Y, You W et al. Clinical and genomic analysis of liver abscess-causing Klebsiella pneumoniae Identifies new liver abscess-associated virulence genes. Front Cell Infect Microbiol 2016; 6:165 [View Article][PubMed]
    [Google Scholar]
  12. Turton JF, Perry C, Elgohari S, Hampton CV. PCR characterization and typing of Klebsiella pneumoniae using capsular type-specific, variable number tandem repeat and virulence gene targets. J Med Microbiol 2010; 59:541–547 [View Article][PubMed]
    [Google Scholar]
  13. Al-Agamy MH, Shibl AM, Elkhizzi NA, Meunier D, Turton JF et al. Persistence of Klebsiella pneumoniae clones with OXA-48 or NDM carbapenemases causing bacteraemias in a Riyadh hospital. Diagn Microbiol Infect Dis 2013; 76:214–216 [View Article][PubMed]
    [Google Scholar]
  14. Brink AA, von Wintersdorff CJ, van der Donk CF, Peeters AM, Beisser PS et al. Development and validation of a single-tube multiple-locus variable number tandem repeat analysis for Klebsiella pneumoniae . PLoS One 2014; 9:e91209 [View Article][PubMed]
    [Google Scholar]
  15. Bialek-Davenet S, Criscuolo A, Ailloud F, Passet V, Nicolas-Chanoine MH et al. Development of a multiplex PCR assay for identification of Klebsiella pneumoniae hypervirulent clones of capsular serotype K2. J Med Microbiol 2014; 63:1608–1614 [View Article][PubMed]
    [Google Scholar]
  16. Compain F, Babosan A, Brisse S, Genel N, Audo J et al. Multiplex PCR for detection of seven virulence factors and K1/K2 capsular serotypes of Klebsiella pneumoniae . J Clin Microbiol 2014; 52:4377–4380 [View Article][PubMed]
    [Google Scholar]
  17. Turton JF, Wright L, Underwood A, Witney AA, Chan YT et al. High-resolution analysis by whole-genome sequencing of an international lineage (Sequence Type 111) of Pseudomonas aeruginosa associated with metallo-carbapenemases in the United Kingdom. J Clin Microbiol 2015; 53:2622–2631 [View Article][PubMed]
    [Google Scholar]
  18. Turton JF, Doumith M, Hopkins KL, Perry C, Meunier D et al. Clonal expansion of Escherichia coli ST38 carrying a chromosomally integrated OXA-48 carbapenemase gene. J Med Microbiol 2016; 65:538–546 [View Article][PubMed]
    [Google Scholar]
  19. 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]
  20. Koren S, Walenz BP, Berlin K, Miller JR, Bergman NH et al. Canu: scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation. Genome Res 2017; 27:722–736 [View Article][PubMed]
    [Google Scholar]
  21. Li H. Minimap and miniasm: fast mapping and de novo assembly for noisy long sequences. Bioinformatics 2016; 32:2103–2110 [View Article][PubMed]
    [Google Scholar]
  22. Kchouk M, Elloumi M. 2017; MiRCA hybrid error correction for minION sequencing long reads. https://github.com/Mkchouk/MiRCA
  23. Milne I, Stephen G, Bayer M, Cock PJ, Pritchard L et al. Using Tablet for visual exploration of second-generation sequencing data. Brief Bioinform 2013; 14:193–202 [View Article][PubMed]
    [Google Scholar]
  24. Ellington MJ, Findlay J, Hopkins KL, Meunier D, Alvarez-Buylla A et al. Multicentre evaluation of a real-time PCR assay to detect genes encoding clinically relevant carbapenemases in cultured bacteria. Int J Antimicrob Agents 2016; 47:151–154 [View Article][PubMed]
    [Google Scholar]
  25. Ellington MJ, Kistler J, Livermore DM, Woodford N. Multiplex PCR for rapid detection of genes encoding acquired metallo-beta-lactamases. J Antimicrob Chemother 2007; 59:321–322 [View Article][PubMed]
    [Google Scholar]
  26. Chuang C, Fan WC, Lin YT, Wang FD. The emergence of Klebsiella pneumoniae liver abscess in non-diabetic patients and the distribution of capsular types. Gut Pathog 2016; 8:46 [View Article][PubMed]
    [Google Scholar]
  27. Iwasaki Y, Inokuchi R, Harada S, Aoki K, Ishii Y et al. Bacterial meningitis caused by hypervirulent Klebsiella pneumoniae capsular genotype K54 with development of granuloma-like nodal enhancement in the brain during the subacute phase. Intern Med 2017; 56:373–376 [View Article][PubMed]
    [Google Scholar]
  28. Turton JF, Englender H, Gabriel SN, Turton SE, Kaufmann ME et al. Genetically similar isolates of Klebsiella pneumoniae serotype K1 causing liver abscesses in three continents. J Med Microbiol 2007; 56:593–597 [View Article][PubMed]
    [Google Scholar]
  29. Fung CP, Lin YT, Lin JC, Chen TL, Yeh KM et al. Klebsiella pneumoniae in gastrointestinal tract and pyogenic liver abscess. Emerg Infect Dis 2012; 18:1322–1325 [View Article][PubMed]
    [Google Scholar]
  30. Siu LK, Yeh KM, Lin JC, Fung CP, Chang FY. Klebsiella pneumoniae liver abscess: a new invasive syndrome. Lancet Infect Dis 2012; 12:881–887 [View Article][PubMed]
    [Google Scholar]
  31. Choi MJ, Ko KS. Loss of hypermucoviscosity and increased fitness cost in colistin-resistant Klebsiella pneumoniae sequence type 23 strains. Antimicrob Agents Chemother 2015; 59:6763–6773 [View Article][PubMed]
    [Google Scholar]
  32. Lam MMC, Wick RR, Wyres KL, Gorrie C, Judd LM et al. Frequent emergence of pathogenic lineages of Klebsiella pneumoniae via mobilisation of yersiniabactin and colibactin. bioRxiv 2017 doi:10.1101/098178
    [Google Scholar]
  33. Struve C, Roe CC, Stegger M, Stahlhut SG, Hansen DS et al. Mapping the Evolution of Hypervirulent Klebsiella pneumoniae . MBio 2015; 6:e00630-15 [View Article][PubMed]
    [Google Scholar]
  34. Wei DD, Wan LG, Deng Q, Liu Y. Emergence of KPC-producing Klebsiella pneumoniae hypervirulent clone of capsular serotype K1 that belongs to sequence type 11 in Mainland China. Diagn Microbiol Infect Dis 2016; 85:192–194 [View Article][PubMed]
    [Google Scholar]
  35. Andrade LN, Vitali L, Gaspar GG, Bellissimo-Rodrigues F, Martinez R et al. Expansion and evolution of a virulent, extensively drug-resistant (polymyxin B-resistant), QnrS1-, CTX-M-2-, and KPC-2-producing Klebsiella pneumoniae ST11 international high-risk clone. J Clin Microbiol 2014; 52:2530–2535 [View Article][PubMed]
    [Google Scholar]
  36. 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 2017 doi:10.1016/S1473-3099(17)30489-9 [View Article][PubMed]
    [Google Scholar]
  37. Gu DX, Huang YL, Ma JH, Zhou HW, Fang Y et al. Detection of colistin resistance gene mcr-1 in hypervirulent Klebsiella pneumoniae and Escherichia coli Isolates from an Infant with Diarrhea in China. Antimicrob Agents Chemother 2016; 60:5099–5100 [View Article][PubMed]
    [Google Scholar]
  38. Chou A, Nuila RE, Franco LM, Stager CE, Atmar RL et al. Prevalence of hypervirulent Klebsiella pneumoniae-associated genes rmpA and magA in two tertiary hospitals in Houston, TX, USA. J Med Microbiol 2016; 65:1047–1048 [View Article][PubMed]
    [Google Scholar]
  39. Peirano G, Pitout JD, Laupland KB, Meatherall B, Gregson DB. Population-based surveillance for hypermucoviscosity Klebsiella pneumoniae causing community-acquired bacteremia in Calgary, Alberta. Can J Infect Dis Med Microbiol 2013; 24:e61e64[PubMed]
    [Google Scholar]
  40. Olaitan AO, Li J. Emergence of polymyxin resistance in Gram-negative bacteria. Int J Antimicrob Agents 2016; 48:581–582 [View Article][PubMed]
    [Google Scholar]
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