Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 26, Number 2—February 2020
Research

Novel Subclone of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 with Enhanced Virulence and Transmissibility, China

Kai Zhou1, Tingting Xiao1, Sophia David1, Qin Wang, Yanzi Zhou, Lihua Guo, David Aanensen, Kathryn E. Holt, Nicholas R. Thomson, Hajo Grundmann2, Ping Shen2, and Yonghong Xiao2Comments to Author 
Author affiliations: First Affiliated Hospital of Southern University of Science and Technology (Shenzhen People’s Hospital); Shenzhen, China (K. Zhou); The Second Clinical Medical College of Jinan University, Shenzhen (K. Zhou); Zhejiang University, Hangzhou, China (T. Xiao, Q. Wang, Y. Zhou, L. Guo, P. Shen, Y. Xiao); Centre for Genomic Pathogen Surveillance, Cambridge, UK (S. David, D. Aanensen); University of Melbourne, Melbourne, Victoria, Australia (K.E. Holt); London School of Hygiene and Tropical Medicine, London, UK (K.E. Holt, N.R. Thomson); Wellcome Trust Sanger Centre, Cambridge (N.R. Thomson); University of Freiburg, Freiburg, Germany (H. Grundmann)

Main Article

Figure 2

Phylogenetic analysis of 216 CRKP ST11 isolates, China, 2013–2017, including 154 CRKP isolates collected during 2012–2017 in study of bloodstream infections in a tertiary hospital and 62 isolates that were sequenced in previous studies (Appendix 2 Table 1). The phylogenetic tree was obtained by mapping all sequence reads to the hybrid assembly of KP47434 and removing the recombined regions from the alignment. The tree was rooted using ST1731 isolate EuSCAPE_ES29 (ERR1541319), which was included

Figure 2. Phylogenetic analysis of 216 CRKP ST11 isolates, China, 2013–2017, including 154 CRKP isolates collected during 2012–2017 in study of bloodstream infections in a tertiary hospital and 62 isolates that were sequenced in previous studies (Appendix 2 Table 1). The phylogenetic tree was obtained by mapping all sequence reads to the hybrid assembly of KP47434 and removing the recombined regions from the alignment. The tree was rooted using ST1731 isolate EuSCAPE_ES29 (ERR1541319), which was included in this analysis but later removed from the tree (a tree including this outgroup is shown in Appendix 1 Figure 1). Five capsular types (KL31, KL47, KL64, KL103, and KL105) were detected in our ST11 collection, which are indicated in different colors as shown in the legend. Some of virulence genes detected are shown here. The rmpA2 gene carried by KL64 isolates was frameshifted, namely rmpA2*. Aerobactin and salmochelin represent the iucABCD-iutA and iroBCDN gene clusters, respectively. The fatal outbreak clone reported in China recently (12) is highlighted on the tree. Lanes: 1, year; 2, country; 3, K-type; 4, rmpA; 5, rmpA2; 6, aerobactin; 7, peg-344; 8, salmochelin; 9, blaKPC. Scale bar indicates single-nucleotide polymorphisms. CRKP, carbapenem-resistant Klebsiella pneumoniae; KL, capsular loci; ST, sequence type.

Main Article

References
  1. Guh  AY, Bulens  SN, Mu  Y, Jacob  JT, Reno  J, Scott  J, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae in 7 US communities, 2012–2013. JAMA. 2015;314:147987. DOIPubMed
  2. Grundmann  H, Glasner  C, Albiger  B, Aanensen  DM, Tomlinson  CT, Andrasević  AT, et al.; European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) Working Group. Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study. Lancet Infect Dis. 2017;17:15363. DOIPubMed
  3. Zhang  R, Liu  L, Zhou  H, Chan  EW, Li  J, Fang  Y, et al. Nationwide surveillance of clinical carbapenem-resistant Enterobacteriaceae (CRE) strains in China. EBioMedicine. 2017;19:98106. DOIPubMed
  4. Patel  G, Huprikar  S, Factor  SH, Jenkins  SG, Calfee  DP. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol. 2008;29:1099106. DOIPubMed
  5. Pitout  JDD, Nordmann  P, Poirel  L. Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrob Agents Chemother. 2015;59:587384. DOIPubMed
  6. Chen  L, Mathema  B, Pitout  JDD, DeLeo  FR, Kreiswirth  BN. Epidemic Klebsiella pneumoniae ST258 is a hybrid strain. MBio. 2014;5:e0135514. DOIPubMed
  7. Gaiarsa  S, Comandatore  F, Gaibani  P, Corbella  M, Dalla Valle  C, Epis  S, et al. Genomic epidemiology of Klebsiella pneumoniae in Italy and novel insights into the origin and global evolution of its resistance to carbapenem antibiotics. Antimicrob Agents Chemother. 2015;59:38996. DOIPubMed
  8. Deleo  FR, Chen  L, Porcella  SF, Martens  CA, Kobayashi  SD, Porter  AR, et al. Molecular dissection of the evolution of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae. Proc Natl Acad Sci U S A. 2014;111:498893. DOIPubMed
  9. Wyres  KL, Gorrie  C, Edwards  DJ, Wertheim  HFL, Hsu  LY, Van Kinh  N, et al. Extensive capsule locus variation and large-scale genomic recombination within the Klebsiella pneumoniae clonal group 258. Genome Biol Evol. 2015;7:126779. DOIPubMed
  10. Jiang  Y, Wei  Z, Wang  Y, Hua  X, Feng  Y, Yu  Y. Tracking a hospital outbreak of KPC-producing ST11 Klebsiella pneumoniae with whole genome sequencing. Clin Microbiol Infect. 2015;21:10017. DOIPubMed
  11. Dong  N, Zhang  R, Liu  L, Li  R, Lin  D, Chan  EW-C, et al. Genome analysis of clinical multilocus sequence Type 11 Klebsiella pneumoniae from China. Microb Genom. 2018;4:5412. DOIPubMed
  12. Gu  D, Dong  N, Zheng  Z, Lin  D, Huang  M, Wang  L, et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis. 2018;18:3746. DOIPubMed
  13. Du  P, Zhang  Y, Chen  C. Emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae. Lancet Infect Dis. 2018;18:234. DOIPubMed
  14. Yao  H, Qin  S, Chen  S, Shen  J, Du  X-D. Emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae. Lancet Infect Dis. 2018;18:25. DOIPubMed
  15. Wong  MHY, Shum  H-P, Chen  JHK, Man  M-Y, Wu  A, Chan  EW-C, et al. Emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae. Lancet Infect Dis. 2018;18:24. DOIPubMed
  16. Xiao  T, Yu  W, Niu  T, Huang  C, Xiao  Y. A retrospective, comparative analysis of risk factors and outcomes in carbapenem-susceptible and carbapenem-nonsusceptible Klebsiella pneumoniae bloodstream infections: tigecycline significantly increases the mortality. Infect Drug Resist. 2018;11:595606. DOIPubMed
  17. Diancourt  L, Passet  V, Verhoef  J, Grimont  PAD, Brisse  S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J Clin Microbiol. 2005;43:417882. DOIPubMed
  18. McLaughlin  MM, Advincula  MR, Malczynski  M, Barajas  G, Qi  C, Scheetz  MH. Quantifying the clinical virulence of Klebsiella pneumoniae producing carbapenemase Klebsiella pneumoniae with a Galleria mellonella model and a pilot study to translate to patient outcomes. BMC Infect Dis. 2014;14:31. DOIPubMed
  19. Naparstek  L, Carmeli  Y, Navon-Venezia  S, Banin  E. Biofilm formation and susceptibility to gentamicin and colistin of extremely drug-resistant KPC-producing Klebsiella pneumoniae. J Antimicrob Chemother. 2014;69:102734. DOIPubMed
  20. Wang  L, Shen  D, Wu  H, Ma  Y. Resistance of hypervirulent Klebsiella pneumoniae to both intracellular and extracellular killing of neutrophils. PLoS One. 2017;12:e0173638. DOIPubMed
  21. Havill  NL, Boyce  JM, Otter  JA. Extended survival of carbapenem-resistant Enterobacteriaceae on dry surfaces. Infect Control Hosp Epidemiol. 2014;35:4457. DOIPubMed
  22. 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. DOIPubMed
  23. Henson  SP, Boinett  CJ, Ellington  MJ, Kagia  N, Mwarumba  S, Nyongesa  S, et al. Molecular epidemiology of Klebsiella pneumoniae invasive infections over a decade at Kilifi County Hospital in Kenya. Int J Med Microbiol. 2017;307:4229. DOIPubMed
  24. Holt  KE, Wertheim  H, Zadoks  RN, Baker  S, Whitehouse  CA, Dance  D, 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:E357481. DOIPubMed
  25. Bowers  JR, Kitchel  B, Driebe  EM, MacCannell  DR, Roe  C, Lemmer  D, et al. Genomic analysis of the emergence and rapid global dissemination of the clonal group 258 Klebsiella pneumoniae pandemic. PLoS One. 2015;10:e0133727. DOIPubMed
  26. Moradigaravand  D, Martin  V, Peacock  SJ, Parkhill  J. Evolution and epidemiology of multidrug-resistant Klebsiella pneumoniae in the United Kingdom and Ireland. MBio. 2017;8:e0197616. DOIPubMed
  27. Didelot  X, Croucher  NJ, Bentley  SD, Harris  SR, Wilson  DJ. Bayesian inference of ancestral dates on bacterial phylogenetic trees. Nucleic Acids Res. 2018;46:e1344. DOIPubMed
  28. Lee  E-M, Ahn  S-H, Park  J-H, Lee  J-H, Ahn  S-C, Kong  I-S. Identification of oligopeptide permease (opp) gene cluster in Vibrio fluvialis and characterization of biofilm production by oppA knockout mutation. FEMS Microbiol Lett. 2004;240:2130. DOIPubMed
  29. Ares  MA, Fernández-Vázquez  JL, Rosales-Reyes  R, Jarillo-Quijada  MD, von Bargen  K, Torres  J, et al. H-NS nucleoid protein controls virulence features of Klebsiella pneumoniae by regulating the expression of type 3 pili and the capsule polysaccharide. Front Cell Infect Microbiol. 2016;6:13. DOIPubMed
  30. Kobayashi  SD, Porter  AR, Freedman  B, Pandey  R, Chen  L, Kreiswirth  BN, et al. Antibody-mediated killing of carbapenem-resistant ST258 Klebsiella pneumoniae by human neutrophils. MBio. 2018;9:1198. DOIPubMed
  31. Pan  Y-J, Lin  T-L, Lin  Y-T, Su  P-A, Chen  C-T, Hsieh  P-F, et al. Identification of capsular types in carbapenem-resistant Klebsiella pneumoniae strains by wzc sequencing and implications for capsule depolymerase treatment. Antimicrob Agents Chemother. 2015;59:103847. DOIPubMed
  32. Koh  TH, Cao  D, Shan  QY, Bacon  A, Hsu  LY, Ooi  EE. Acquired carbapenemases in Enterobactericeae in Singapore, 1996-2012. Pathology. 2013;45:6003. DOIPubMed
  33. Cryz  SJ Jr, Mortimer  PM, Mansfield  V, Germanier  R. Seroepidemiology of Klebsiella bacteremic isolates and implications for vaccine development. J Clin Microbiol. 1986;23:68790. DOIPubMed
  34. Jones  CL, Clancy  M, Honnold  C, Singh  S, Snesrud  E, Onmus-Leone  F, et al. Fatal outbreak of an emerging clone of extensively drug-resistant Acinetobacter baumannii with enhanced virulence. Clin Infect Dis. 2015;61:14554. DOIPubMed
  35. Melin  M, Trzciński  K, Meri  S, Käyhty  H, Väkeväinen  M. The capsular serotype of Streptococcus pneumoniae is more important than the genetic background for resistance to complement. Infect Immun. 2010;78:526270. DOIPubMed
  36. Rukke  HV, Kalluru  RS, Repnik  U, Gerlini  A, José  RJ, Periselneris  J, et al. Protective role of the capsule and impact of serotype 4 switching on Streptococcus mitis. Infect Immun. 2014;82:3790801. DOIPubMed
  37. Struve  C, Roe  CC, Stegger  M, Stahlhut  SG, Hansen  DS, Engelthaler  DM, et al. Mapping the evolution of hypervirulent Klebsiella pneumoniae. MBio. 2015;6:e00630. DOIPubMed
  38. Hsu  C-R, Lin  T-L, Chen  Y-C, Chou  H-C, Wang  J-T. The role of Klebsiella pneumoniae rmpA in capsular polysaccharide synthesis and virulence revisited. Microbiology. 2011;157:344657. DOIPubMed

Main Article

1These first authors contributed equally to this article.

2These senior authors contributed equally to this article.

Page created: January 17, 2020
Page updated: January 17, 2020
Page reviewed: January 17, 2020
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external