1887

Abstract

is a frequent cause of nosocomial and severe community-acquired infections. Multidrug-resistant (MDR) and hypervirulent (hv) strains represent major threats, and tracking their emergence, evolution and the emerging convergence of MDR and hv traits is of major importance. We employed whole-genome sequencing (WGS) to study the evolution and epidemiology of a large longitudinal collection of clinical isolates from the H301 hospital in Beijing, China. Overall, the population was highly diverse, although some clones were predominant. Strains belonging to clonal group (CG) 258 were dominant, and represented the majority of carbapenemase-producers. While CG258 strains showed high diversity, one clone, ST11-KL47, represented the majority of isolates, and was highly associated with the KPC-2 carbapenemase and several virulence factors, including a virulence plasmid. The second dominant clone was CG23, which is the major hv clone globally. While it is usually susceptible to multiple antibiotics, we found some isolates harbouring MDR plasmids encoding for ESBLs and carbapenemases. We also reported the local emergence of a recently described high-risk clone, ST383. Conversely to strains belonging to CG258, which are usually associated to KPC-2, ST383 strains seem to readily acquire carbapenemases of different types. Moreover, we found several ST383 strains carrying the hypervirulence plasmid. Overall, we detected about 5 % of simultaneous carriage of AMR genes (ESBLs or carbapenemases) and hypervirulence genes. Tracking the emergence and evolution of such strains, causing severe infections with limited treatment options, is fundamental in order to understand their origin and evolution and to limit their spread. This article contains data hosted by Microreact.

Funding
This study was supported by the:
  • ND4ID (Award 675412)
    • Principle Award Recipient: MattiaPalmieri
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2021-02-25
2021-10-28
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References

  1. 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]
  2. Struve C, Roe CC, Stegger M, Stahlhut SG, Hansen DS et al. Mapping the evolution of hypervirulent Klebsiella pneumoniae. mBio 2015; 6:e00630 [View Article][PubMed]
    [Google Scholar]
  3. Zhang R, Liu L, Zhou H, Chan EW, Li J et al. Nationwide surveillance of clinical carbapenem-resistant Enterobacteriaceae (CRE) Strains in China. EBioMedicine 2017; 19:98–106 [View Article][PubMed]
    [Google Scholar]
  4. Shon AS, Bajwa RPS, Hypervirulent RTA. hypermucoviscous) Klebsiella pneumoniae. Virulence 2013; 4:107–118
    [Google Scholar]
  5. Kabha K, Nissimov L, Athamna A, Keisari Y, Parolis H et al. Relationships among capsular structure, phagocytosis, and mouse virulence in Klebsiella pneumoniae. Infect Immun 1995; 63:847–852 [View Article][PubMed]
    [Google Scholar]
  6. Lam MMC, Wick RR, Wyres KL, Gorrie CL, Judd LM et al. Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations. Microb Genom 2018; 4:e000196 [View Article][PubMed]
    [Google Scholar]
  7. Lam MMC, Wyres KL, Judd LM, Wick RR, Jenney A et al. Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae. Genome Med 2018; 10:77 [View Article][PubMed]
    [Google Scholar]
  8. Siu LK, Yeh K-M, Lin J-C, Fung C-P, Chang F-Y. Klebsiella pneumoniae liver abscess: a new invasive syndrome. Lancet Infect Dis 2012; 12:881–887 [View Article][PubMed]
    [Google Scholar]
  9. Bialek-Davenet S, Criscuolo A, Ailloud F, Passet V, Jones L et al. Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg Infect Dis 2014; 20:1812–1820 [View Article][PubMed]
    [Google Scholar]
  10. Liu Y, Liu P-P, Wang L-H, Wei D-D, Wan L-G et al. Capsular polysaccharide types and virulence-related traits of epidemic KPC-Producing Klebsiella pneumoniae isolates in a Chinese University Hospital. Microb Drug Resist 2017; 23:901–907 [View Article][PubMed]
    [Google Scholar]
  11. Shen D, Ma G, Li C, Jia X, Qin C et al. Emergence of a multidrug-resistant hypervirulent Klebsiella pneumoniae sequence Type 23 strain with a rare blaCTX-M-24-harboring virulence plasmid. Antimicrob Agents Chemother 2019; 63:e02273–18 [View Article][PubMed]
    [Google Scholar]
  12. Dong N, Lin D, Zhang R, Chan EW-C, Chen S. Carriage of blaKPC-2 by a virulence plasmid in hypervirulent Klebsiella pneumoniae. J Antimicrob Chemother 2018; 73:3317–3321 [View Article][PubMed]
    [Google Scholar]
  13. Chen Y, Marimuthu K, Teo J, Venkatachalam I, Cherng BPZ et al. Acquisition of Plasmid with Carbapenem-Resistance Gene blaKPC2 in Hypervirulent Klebsiella pneumoniae, Singapore. Emerg Infect Dis 2020; 26:549–559 [View Article][PubMed]
    [Google Scholar]
  14. Hu F-P, Guo Y, Zhu D-M, Wang F, Jiang X-F et al. Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005-2014. Clin Microbiol Infect 2016; 22 Suppl 1:S9–S14 [View Article][PubMed]
    [Google Scholar]
  15. Hu F, Guo Y, Yang Y, Zheng Y, Wu S et al. Resistance reported from China antimicrobial surveillance network (CHINET) in 2018. Eur J Clin Microbiol Infect Dis 2019; 38:2275–2281 [View Article][PubMed]
    [Google Scholar]
  16. Zhang Y, Wang Q, Yin Y, Chen H, Jin L. Epidemiology of carbapenem-resistant Enterobacteriaceae infections: Report from the China CRE Network. Antimicrob Agents Chemother 2018; Jan 25;62:e01882–17
    [Google Scholar]
  17. Chen L, Mathema B, Chavda KD, DeLeo FR, Bonomo RA et al. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. Trends Microbiol 2014; 22:686–696 [View Article]
    [Google Scholar]
  18. Dong N, Zhang R, Liu L, Li R, Lin D et al. Genome analysis of clinical multilocus sequence Type 11 Klebsiella pneumoniae from China. Microb Genomics 2018; 4:e000149 [View Article]
    [Google Scholar]
  19. Zhou K, Xiao T, David S, Wang Q, Zhou Y et al. Novel subclone of carbapenem-resistant Klebsiella pneumoniae sequence Type 11 with enhanced virulence and transmissibility, China. Emerg Infect Dis 2020; 26:289–297 [View Article]
    [Google Scholar]
  20. 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]
    [Google Scholar]
  21. Yao H, Qin S, Chen S, Shen J, Du X-D. Emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae. Lancet Infect Dis 2018; 18:25 [View Article]
    [Google Scholar]
  22. Wong MHY, Shum H-P, Chen JHK, Man M-Y, Wu A et al. Emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae. Lancet Infect Dis 2018; 18:24 [View Article]
    [Google Scholar]
  23. Xu M, Fu Y, Fang Y, Xu H, Kong H et al. High prevalence of KPC-2-producing hypervirulent Klebsiella pneumoniae causing meningitis in Eastern China. Infect Drug Resist 2019; 12:641–653 [View Article]
    [Google Scholar]
  24. Zhang Y, Jin L, Ouyang P, Wang Q, Wang R et al. Evolution of hypervirulence in carbapenem-resistant Klebsiella pneumoniae in China: a multicentre, molecular epidemiological analysis. J Antimicrob Chemother 2020; 75:327–336 [View Article]
    [Google Scholar]
  25. Yang Q, Jia X, Zhou M, Zhang H, Yang W et al. Emergence of ST11-K47 and ST11-K64 hypervirulent carbapenem-resistant Klebsiella pneumoniae in bacterial liver abscesses from China: a molecular, biological, and epidemiological study. Emerg Microbes Infect 2020; 9:320–331 [View Article]
    [Google Scholar]
  26. van Dorp L, Wang Q, Shaw LP, Acman M, Brynildsrud OB et al. Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains. Microb Genomics 2019; 5:1–11 [View Article]
    [Google Scholar]
  27. EUCAST The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 9.0, 2019. http://www.eucast.org.
  28. Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18:268–281 [View Article]
    [Google Scholar]
  29. 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]
  30. Wick RR, Schultz MB, Zobel J, Holt KE. Bandage: interactive visualization of de novo genome assemblies: Fig. 1. Bioinformatics 2015; 31:3350–3352 [View Article]
    [Google Scholar]
  31. Diancourt L, Passet V, Verhoef J, Grimont PAD, Brisse S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J Clin Microbiol 2005; 43:4178–4182 [View Article]
    [Google Scholar]
  32. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 2012; 67:2640–2644 [View Article]
    [Google Scholar]
  33. 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]
    [Google Scholar]
  34. Wyres KL, Wick RR, Gorrie C, Jenney A, Follador R et al. Identification of Klebsiella capsule synthesis loci from whole genome data. Microb Genomics 2016; 2:e000102 [View Article]
    [Google Scholar]
  35. 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]
    [Google Scholar]
  36. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 2014; 30:1312–1313 [View Article]
    [Google Scholar]
  37. Argimón S, Abudahab K, Goater RJE, Fedosejev A, Bhai J et al. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microb genomics 2016; 2:e000093 [View Article]
    [Google Scholar]
  38. Hadfield J, Croucher NJ, Goater RJ, Abudahab K, Aanensen DM et al. Phandango: an interactive viewer for bacterial population genomics. Bioinformatics 2018; 34:292–293 [View Article]
    [Google Scholar]
  39. Letunic I, Bork P. Interactive tree of life (iTOL) V3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res 2016; 44:W242–W245 [View Article]
    [Google Scholar]
  40. Treangen TJ, Ondov BD, Koren S, Phillippy AM. The harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol 2014; 15:524 [View Article]
    [Google Scholar]
  41. Liao CH, Huang YT, Chang CY, Hsu HS, Hsueh PR. Capsular serotypes and multilocus sequence types of bacteremic Klebsiella pneumoniae isolates associated with different types of infections. Eur J Clin Microbiol Infect Dis 2014; 33:365–369 [View Article]
    [Google Scholar]
  42. Ardanuy C, Liñares J, Domínguez María Angeles, Hernández-Allés S, Benedí VJ et al. Outer membrane profiles of clonally related Klebsiella pneumoniae isolates from clinical samples and activities of cephalosporins and carbapenems. Antimicrob Agents Chemother 1998; 42:1636–1640 [View Article]
    [Google Scholar]
  43. Zhao F, Feng Y, X, McNally A, Zong Z. Remarkable diversity of escherichia coli carrying mcr-1 from hospital sewage with the identification of two new mcr-1 variants. Front Microbiol 2094; 2017:8
    [Google Scholar]
  44. Lam MMC, Wick RR, Wyres KL, Gorrie CL, Judd LM et al. Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations. Microb Genom 2018; 4:e000196 [View Article][PubMed]
    [Google Scholar]
  45. Zhao J, Liu C, Liu Y, Zhang Y, Xiong Z et al. Genomic characteristics of clinically important ST11 Klebsiella pneumoniae strains worldwide. J Glob Antimicrob Resist 2020; 22:519–526 [View Article]
    [Google Scholar]
  46. Liu P, Li P, Jiang X, Bi D, Xie Y et al. Complete genome sequence of Klebsiella pneumoniae subsp. pneumoniae HS11286, a multidrug-resistant strain isolated from human sputum. J Bacteriol 2012; 194:1841–1842 [View Article]
    [Google Scholar]
  47. MMC L, Wyres KL, Duchêne S, Wick RR, Judd LM. Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination. Nat Commun 2018; 9:2703
    [Google Scholar]
  48. Liu YM, Li BB, Zhang YY, Zhang W, Shen H et al. Clinical and molecular characteristics of emerging hypervirulent Klebsiella pneumoniae bloodstream infections in mainland China. Antimicrob Agents Chemother 2014; 58:5379–5385 [View Article]
    [Google Scholar]
  49. Li C, Ma G, Yang T, Wen X, Qin C et al. A rare carbapenem-resistant hypervirulent K1/ST1265 Klebsiella pneumoniae with an untypeable blaKPC-harboured conjugative plasmid. J Glob Antimicrob Resist 2020; 22:426–433 [View Article]
    [Google Scholar]
  50. Wang Y, Lo W-U, Lai RW-M, Tse CW-S, Lee RA et al. IncN ST7 epidemic plasmid carrying bla IMP-4 in Enterobacteriaceae isolates with epidemiological links to multiple geographical areas in China. J Antimicrob Chemother 2017; 72:99–103 [View Article]
    [Google Scholar]
  51. Gołebiewski M, Kern-Zdanowicz I, Zienkiewicz M, Adamczyk M, Zylinska J et al. Complete nucleotide sequence of the pCTX-M3 plasmid and its involvement in spread of the extended-spectrum beta-lactamase gene blaCTX-M-3. Antimicrob Agents Chemother 2007; 51:3789–3795 [View Article][PubMed]
    [Google Scholar]
  52. Turton J, Davies F, Turton J, Perry C, Payne Z et al. Hybrid resistance and virulence plasmids in “high-risk” clones of klebsiella pneumoniae, including those carrying blaNDM-5. Microorganisms 2019; 7:326 [View Article]
    [Google Scholar]
  53. Wyres KL, Wick RR, Judd LM, Froumine R, Tokolyi A et al. Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae. PLoS Genet 2019; 15:e1008114 [View Article]
    [Google Scholar]
  54. CARSS China Antimicrobial Resistance Surveillance System. Available at: http://www. carss.cn/. Accessed 31 March 2020.
  55. Long SW, Olsen RJ, Eagar TN, Beres SB, Zhao P. Population genomic analysis of 1,777 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates, Houston, Texas: Unexpected abundance of clonal group 307. mBio 201; 7 May 16;8:e00489–17
    [Google Scholar]
  56. 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]
    [Google Scholar]
  57. Geraci DM, Bonura C, Giuffrè M, Saporito L, Graziano G et al. Is the monoclonal spread of the ST258, KPC-3-producing clone being replaced in southern Italy by the dissemination of multiple clones of carbapenem-nonsusceptible, KPC-3-producing Klebsiella pneumoniae?. Clinical Microbiology and Infection 2015; 21:e15–e17 [View Article]
    [Google Scholar]
  58. Hu F, Zhu D, Wang F, Wang M. Current status and trends of antibacterial resistance in China; 2018; 67128–134
  59. 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 U S A 2015; 112:E3574–E3581 [View Article]
    [Google Scholar]
  60. Russo TA, Olson R, MacDonald U, Metzger D, Maltese LM et al. Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae. Infect Immun 2014; 82:2356–2367 [View Article]
    [Google Scholar]
  61. Russo TA, Olson R, Fang CT, Stoesser N, Miller M. Identification of biomarkers for differentiation of hypervirulent Klebsiella pneumoniae from classical K. pneumoniae. J Clin Microbiol 2018; Aug 27;56:e00776–18
    [Google Scholar]
  62. Shankar C, Nabarro LEB, Devanga Ragupathi NK, Muthuirulandi Sethuvel DP, Daniel JLK. Draft genome sequences of three hypervirulent carbapenem-Resistant Klebsiella pneumoniae isolates from bacteremia. Genome Announc 2016; Nov-Dec; 4:
    [Google Scholar]
  63. Wong MHY, Shum H-P, Chen JHK, Man M-Y, Wu A. Emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae. Lancet Infect Dis 2017; 3099:5–6
    [Google Scholar]
  64. Du P, Zhang Y, Chen C. Emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae. Lancet Infect Dis 2018; 18:23–24 [View Article]
    [Google Scholar]
  65. Wyres KL, Nguyen TNT, Lam MMC, Judd LM, van Vinh Chau N et al. Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia. Genome Med 2020; 12:11 [View Article]
    [Google Scholar]
  66. Papagiannitsis CC, Giakkoupi P, Vatopoulos AC, Tryfinopoulou K, Miriagou V et al. Emergence of Klebsiella pneumoniae of a novel sequence type (ST383) producing VIM-4, KPC-2 and CMY-4 β-lactamases. Int J Antimicrob Agents 2010; 36:573–574 [View Article]
    [Google Scholar]
  67. Dimou V, Dhanji H, Pike R, Livermore DM, Woodford N. Characterization of Enterobacteriaceae producing OXA-48-like carbapenemases in the UK. J Antimicrob Chemother 2012; 67:1660–1665 [View Article]
    [Google Scholar]
  68. Guo L, An J, Ma Y, Ye L, Luo Y et al. Nosocomial Outbreak of OXA-48-Producing Klebsiella pneumoniae in a Chinese Hospital: Clonal Transmission of ST147 and ST383. PLoS One 2016; 11:e0160754 [View Article]
    [Google Scholar]
  69. Turton JF, Payne Z, Coward A, Hopkins KL, Turton JA et al. Virulence genes in isolates of Klebsiella pneumoniae from the UK during 2016, including among carbapenemase gene-positive hypervirulent K1-ST23 and ‘non-hypervirulent’ types ST147, ST15 and ST383. J Med Microbiol 2018; 67:118–128 [View Article]
    [Google Scholar]
  70. Chen L, Kreiswirth BN. Convergence of carbapenem-resistance and hypervirulence in Klebsiella pneumoniae. Lancet Infect Dis 2017; 3099:9–10
    [Google Scholar]
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