Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Population genomics of Klebsiella pneumoniae

Abstract

Klebsiella pneumoniae is a common cause of antimicrobial-resistant opportunistic infections in hospitalized patients. The species is naturally resistant to penicillins, and members of the population often carry acquired resistance to multiple antimicrobials. However, knowledge of K. pneumoniae ecology, population structure or pathogenicity is relatively limited. Over the past decade, K. pneumoniae has emerged as a major clinical and public health threat owing to increasing prevalence of healthcare-associated infections caused by multidrug-resistant strains producing extended-spectrum β-lactamases and/or carbapenemases. A parallel phenomenon of severe community-acquired infections caused by ‘hypervirulent’ K. pneumoniae has also emerged, associated with strains expressing acquired virulence factors. These distinct clinical concerns have stimulated renewed interest in K. pneumoniae research and particularly the application of genomics. In this Review, we discuss how genomics approaches have advanced our understanding of K. pneumoniae taxonomy, ecology and evolution as well as the diversity and distribution of clinically relevant determinants of pathogenicity and antimicrobial resistance. A deeper understanding of K. pneumoniae population structure and diversity will be important for the proper design and interpretation of experimental studies, for interpreting clinical and public health surveillance data and for the design and implementation of novel control strategies against this important pathogen.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Taxonomic position of Klebsiella pneumoniae.
Fig. 2: Klebsiella pneumoniae population structure and global problem clones.
Fig. 3: Geographical distribution of Klebsiella pneumoniae clones harbouring resistance to carbapenems and third-generation cephalosporins.
Fig. 4: Antimicrobial resistance in Klebsiella pneumoniae.

Similar content being viewed by others

References

  1. Adeolu, M., Alnajar, S., Naushad, S. & Gupta, R. S. Genome-based phylogeny and taxonomy of the ‘Enterobacteriales’: proposal for Enterobacterales ord. nov. divided into the families Enterobacteriaceae, Erwiniaceae fam. nov., Pectobacteriaceae fam. nov., Yersiniaceae fam. nov., Hafniaceae fam. nov., Morganellaceae fam. nov., and Budviciaceae fam. nov. Int. J. Syst. Evol. Microbiol. 66, 5575–5599 (2016).

    CAS  PubMed  Google Scholar 

  2. Pendleton, J. N., Gorman, S. P. & Gilmore, B. F. Clinical relevance of the ESKAPE pathogens. Expert. Rev. Anti Infect. Ther. 11, 297–308 (2013).

    CAS  PubMed  Google Scholar 

  3. Okomo, U. et al. Aetiology of invasive bacterial infection and antimicrobial resistance in neonates in sub-Saharan Africa: a systematic review and meta-analysis in line with the STROBE-NI reporting guidelines. Lancet Infect. Dis. 19, 1219–1234 (2019).

    CAS  PubMed  Google Scholar 

  4. Zaidi, A. K. M. et al. Hospital-acquired neonatal infections in developing countries. Lancet 365, 1175–1188 (2005).

    PubMed  Google Scholar 

  5. World Health Organization. Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Development of New Antibiotics (WHO, 2017).

  6. Cassini, 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. 19, 56–66 (2019).

    PubMed  PubMed Central  Google Scholar 

  7. Musicha, P. et al. Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study. Lancet. Infect. Dis. 17, 1042–1052 (2017).

    PubMed  PubMed Central  Google Scholar 

  8. Bagley, S. T. Habitat association of Klebsiella species. Infect. Contr. 6, 52–58 (1985).

    CAS  Google Scholar 

  9. Holt, K. E. 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 112, E3574–E3581 (2015). This large-scale comparative genomics study of diverse K. pneumoniae and related members of the species complex from seven countries establishes the global genomic framework and the scale and heterogeneity of the pan-genome, and identifies genetic loci that are statistically associated with invasive disease versus asymptomatic colonization in humans.

    CAS  PubMed  Google Scholar 

  10. Wyres, K. L. et al. Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae. PLoS Genet. 15, e1008114 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Gu, D. et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect. Dis. 3099, 1–10 (2017). This study presents an initial report of MDR-ST11 harbouring a KpVP-1 virulence plasmid variant, which displays enhanced survival in a human neutrophil assay and enhanced virulence in the Galleria mellonella infection model in comparison with typical MDR-ST11.

    Google Scholar 

  12. Lam, M. M. C. et al. Convergence of virulence and MDR in a single plasmid vector in MDR Klebsiella pneumoniae ST15. J. Antimicrob. Chemother. 74, 1218–1222 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Long, S. W. et al. Whole-genome sequencing of human clinical Klebsiella pneumoniae isolates reveals misidentification and misunderstandings of Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae. mSphere 2, e00290–e00317 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Gorrie, C. L. et al. Gastrointestinal carriage is a major reservoir of K. pneumoniae infection in intensive care patients. Clin. Infect. Dis. 65, 208–215 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Rodrigues, C., Passet, V., Rakotondrasoa, A. & Brisse, S. Identification of Klebsiella pneumoniae, Klebsiella quasipneumoniae, Klebsiella variicola and related phylogroups by MALDI-TOF mass spectrometry. Front. Microbiol. 9, 1–7 (2018).

    Google Scholar 

  16. Long, S. W. et al. Population genomic analysis of 1,777 extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates, Houston, Texas: unexpected abundance of clonal group 307. mBio 8, e00489–e00517 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Henson, S. P. et al. Molecular epidemiology of Klebsiella pneumoniae invasive infections over a decade at Kilifi County Hospital in Kenya. Int. J. Med. Microbiol. 307, 422–429 (2017).

    PubMed  PubMed Central  Google Scholar 

  18. Heinz, E. et al. Resistance mechanisms and population structure of highly drug resistant Klebsiella in Pakistan during the introduction of the carbapenemase NDM-1. Sci. Rep. 9, 2392 (2019).

    PubMed  PubMed Central  Google Scholar 

  19. Gorrie, C. L. et al. Antimicrobial resistant Klebsiella pneumoniae carriage and infection in specialized geriatric care wards linked to acquisition in the referring hospital. Clin. Infect. Dis. 67, 161–170 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Wyres, K. L. & Holt, K. E. Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria. Curr. Opin. Microbiol. 45, 131–139 (2018).

    CAS  PubMed  Google Scholar 

  21. Marques, C. et al. Evidence of Klebsiella pneumoniae sharing between healthy companion animals and co-habiting humans. J. Clin. Microbiol. 57, e01537–e01618 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Zadoks, R. N. et al. Sources of Klebsiella and Raoultella species on dairy farms: be careful where you walk. J. Dairy Sci. 94, 1045–1051 (2011).

    CAS  PubMed  Google Scholar 

  23. Conlan, S., Kong, H. H. & Segre, J. A. Species-level analysis of DNA sequence data from the NIH human microbiome project. PLoS One 7, e47075 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Martin, R. M. et al. Molecular epidemiology of colonizing and infecting isolates of Klebsiella pneumoniae. mSphere 1, e00261–e00316 (2016).

    PubMed  PubMed Central  Google Scholar 

  25. Ludden, C. et al. A One Health study of the genetic relatedness of Klebsiella pneumoniae and their mobile elements in the East of England. Clin. Infect. Dis. 70, 219–226 (2020).

    PubMed  Google Scholar 

  26. Chung, D. R. et al. Fecal carriage of serotype K1 Klebsiella pneumoniae ST23 strains closely related to liver abscess isolates in Koreans living in Korea. Eur. J. Clin. Microbiol. Infect. Dis. 31, 481–486 (2012).

    CAS  PubMed  Google Scholar 

  27. Lin, Y.-T. et al. Seroepidemiology of Klebsiella pneumoniae colonizing the intestinal tract of healthy Chinese and overseas Chinese adults in Asian countries. BMC Microbiol. 12, 13 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Löhr, I. H. et al. Long-term faecal carriage in infants and intra-household transmission of CTX-M-15-producing Klebsiella pneumoniae following a nosocomial outbreak. J. Antimicrob. Chemother. 68, 1043–1048 (2013).

    PubMed  Google Scholar 

  29. Mo, Y. et al. Carriage duration of carbapenemase-producing Enterobacteriaceae in a hospital cohort—implications for infection control measures. medRxiv. https://doi.org/10.1101/19001479 (2019).

    Article  Google Scholar 

  30. Podschun, R. & Ullmann, U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin. Microbiol. Rev. 11, 589–603 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Shimasaki, T. et al. Increased relative abundance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae within the gut microbiota is associated with risk of bloodstream infection in long-term acute care hospital patients. Clin. Infect. Dis. 68, 2053–2059 (2019).

    PubMed  Google Scholar 

  32. Xu, L., Sun, X. & Ma, X. Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann. Clin. Microbiol. Antimicrob. 16, 18 (2017).

    PubMed  PubMed Central  Google Scholar 

  33. Bassetti, M., Peghin, M., Vena, A. & Giacobbe, D. R. Treatment of infections due to MDR Gram-negative bacteria. Front. Med. 6, 74 (2019).

    Google Scholar 

  34. Manohar, P., Tamhankar, A. J., Lundborg, C. S. & Nachimuthu, R. Therapeutic characterization and efficacy of bacteriophage cocktails infecting Escherichia coli, Klebsiella pneumoniae, and Enterobacter species. Front. Microbiol. 10, 574 (2019).

    PubMed  PubMed Central  Google Scholar 

  35. Meatherall, B. L., Gregson, D., Ross, T., Pitout, J. D. D. & Laupland, K. B. Incidence, risk factors, and outcomes of Klebsiella pneumoniae bacteremia. Am. J. Med. 122, 866–873 (2009).

    PubMed  Google Scholar 

  36. Russo, T. A. & Marr, C. M. Hypervirulent Klebsiella pneumoniae. Clin. Microbiol. Rev. 32, e00001–e00019 (2019).

    PubMed  Google Scholar 

  37. Ko, W. C. et al. Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerg. Infect. Dis. 8, 160–166 (2002).

    PubMed  PubMed Central  Google Scholar 

  38. Kim, J. K., Chung, D. R., Wie, S. H., Yoo, J. H. & Park, S. W. Risk factor analysis of invasive liver abscess caused by the K1 serotype Klebsiella pneumoniae. Eur. J. Clin. Microbiol. Infect. Dis. 28, 109–111 (2009).

    PubMed  Google Scholar 

  39. Brockhurst, M. A. et al. The ecology and evolution of pangenomes. Curr. Biol. 29, R1094–R1103 (2019).

    CAS  PubMed  Google Scholar 

  40. Bialek-Davenet, S. et al. Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerg. Infect. Dis. 20, 1812–1820 (2014). This work establishes the cgMLST scheme for K. pneumoniae and the associated species complex, which is based on 694 core genes and is available through the BIGSdb-Kp online database.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Diancourt, L., Passet, V., Verhoef, J., Grimont, P. A. & Brisse, S. Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J. Clin. Microbiol. 43, 4178–4182 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Brisse, S. et al. Virulent clones of Klebsiella pneumoniae: identification and evolutionary scenario based on genomic and phenotypic characterization. PLoS One 4, e4982 (2009).

    PubMed  PubMed Central  Google Scholar 

  43. Breurec, S. et al. Klebsiella pneumoniae resistant to third-generation cephalosporins in five African and two Vietnamese major towns: multiclonal population structure with two major international clonal groups, CG15 and CG258. Clin. Microbiol. Infect. 19, 349–355 (2013).

    CAS  PubMed  Google Scholar 

  44. McInerney, J. O., McNally, A. & O’Connell, M. J. Why prokaryotes have pangenomes. Nat. Microbiol. 2, 17040 (2017).

    CAS  PubMed  Google Scholar 

  45. Wyres, K. L. et al. Extensive capsule locus variation and large-scale genomic recombination within the Klebsiella pneumoniae clonal group 258. Genome Biol. Evol. 7, 1267–1279 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Lam, M. M. C. et al. Population genomics of hypervirulent Klebsiella pneumoniae clonal group 23 reveals early emergence and rapid global dissemination. Nat. Commun. 9, 2703 (2018).

    PubMed  PubMed Central  Google Scholar 

  47. Bowers, J. R. et al. Genomic analysis of the emergence and rapid global dissemination of the clonal group 258 Klebsiella pneumoniae pandemic. PLoS One 10, e0133727 (2015).

    PubMed  PubMed Central  Google Scholar 

  48. Navon-Venezia, S., Kondratyeva, K. & Carattoli, A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol. Rev. 41, 252–275 (2017).

    CAS  PubMed  Google Scholar 

  49. Conlan, S. et al. Plasmid dynamics in KPC-positive Klebsiella pneumoniae during long-term patient colonization. mBio 7, e00742–e00816 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Shen, J., Lv, L., Wang, X., Xiu, Z. & Chen, G. Comparative analysis of CRISPR–Cas systems in Klebsiella genomes. J. Basic. Microbiol. 57, 325–336 (2017).

    CAS  PubMed  Google Scholar 

  51. Ellington, M. J. et al. Contrasting patterns of longitudinal population dynamics and antimicrobial resistance mechanisms in two priority bacterial pathogens over 7 years in a single center. Genome Biol. 20, 184 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Wyres, K. L. & Holt, K. E. Klebsiella pneumoniae population genomics and antimicrobial-resistant clones. Trends Microbiol. 24, 944–956 (2016).

    CAS  PubMed  Google Scholar 

  53. Wyres, K. L. et al. Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307. J. Antimicrob. Chemother. 74, 577–581 (2019).

    CAS  PubMed  Google Scholar 

  54. David, S. et al. Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread. Nat. Microbiol. 4, 1919–1929 (2019). This study is a genomic analysis of >1,700 CRKp and carbapenem-susceptible K. pneumoniae infections isolated from patients in 244 hospitals in 32 countries across Europe, providing the first large-scale systematic sample for comparison of clone and resistance gene distributions.

    CAS  PubMed  Google Scholar 

  55. Turton, J. F. 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. 67, 118–128 (2017).

    PubMed  Google Scholar 

  56. Siu, L. K. et al. Molecular typing and virulence analysis of serotype K1 Klebsiella pneumoniae strains isolated from liver abscess patients and stool samples from noninfectious subjects in Hong Kong, Singapore, and Taiwan. J. Clin. Microbiol. 49, 3761–3765 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Lin, J. C. et al. Genotypes and virulence in serotype K2 Klebsiella pneumoniae from liver abscess and non-infectious carriers in Hong Kong, Singapore and Taiwan. Gut Pathog. 12, 21 (2014).

    Google Scholar 

  58. Shi, Q. et al. Diversity of virulence level phenotype of hypervirulent Klebsiella pneumoniae from different sequence type lineage. BMC Microbiol. 18, 1–6 (2018).

    Google Scholar 

  59. Lee, I. R. et al. Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population. Sci. Rep. 13, 29316 (2016).

    Google Scholar 

  60. Zhang, Y. et al. High prevalence of hypervirulent Klebsiella pneumoniae infection in China: geographic distribution, clinical characteristics, and antimicrobial resistance. Antimicrob. Agents Chemother. 60, 6115–6120 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Wyres, K. L. et al. Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia. Genomic med. 12, 11 (2019).

    Google Scholar 

  62. Heinz, E., Brindle, R., Morgan-McCalla, A., Peters, K. & Thomson, N. R. Caribbean multi-centre study of Klebsiella pneumoniae: whole genome sequencing, antimicrobial resistance and virulence factors. Microb. Genomics. 5, e000266 (2019).

    Google Scholar 

  63. Musicha, P. et al. Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages. J. Antimicrob. Chemother. 74, 1223–1232 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhang, R. et al. Presence of NDM in non-E. coli Enterobacteriaceae in the poultry production environment. J. Antimicrob. Chemother. 74, 2209–2213 (2019).

    CAS  PubMed  Google Scholar 

  65. Marques, C. et al. Klebsiella pneumoniae causing urinary tract infections in companion animals and humans: population structure, antimicrobial resistance and virulence genes. J. Antimicrob. Chemother. 74, 594–602 (2019).

    CAS  PubMed  Google Scholar 

  66. Anzai, E. K. et al. First case report of non-human primates (Alouatta clamitans) with the hypervirulent Klebsiella pneumoniae serotype K1 strain ST23: a possible emerging wildlife pathogen. J. Med. Primatol. 46, 337–342 (2017).

    CAS  PubMed  Google Scholar 

  67. Bowring, B. G., Fahy, V. A., Morris, A. & Collins, A. M. An unusual culprit: Klebsiella pneumoniae causing septicaemia outbreaks in neonatal pigs? Vet. Microbiol. 203, 267–270 (2017).

    PubMed  Google Scholar 

  68. Runcharoen, C. et al. Whole genome sequencing reveals high-resolution epidemiological links between clinical and environmental Klebsiella pneumoniae. Genome Med. 9, 6 (2017).

    PubMed  PubMed Central  Google Scholar 

  69. Davis, G. S. et al. Intermingled Klebsiella pneumoniae populations between retail meats and human urinary tract infections. Clin. Infect. Dis. 61, 892–899 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Singh, A., Lekshmi, M., Prakasan, S., Nayak, B. & Kumar, S. Multiple antibiotic-resistant, extended spectrum-β-lactamase (ESBL)-producing Enterobacteria in fresh seafood. Microorganisms 5, E53 (2017).

    Google Scholar 

  71. Zekar, F. M. et al. From farms to markets: Gram-negative bacteria resistant to third-generation cephalosporins in fruits and vegetables in a region of North Africa. Front. Microbiol. 8, 1569 (2017).

    Google Scholar 

  72. Yaici, L. et al. Spread of ESBL/AmpC-producing Escherichia coli and Klebsiella pneumoniae in the community through ready-to-eat sandwiches in Algeria. Int. J. Food Microbiol. 245, 66–72 (2017).

    CAS  PubMed  Google Scholar 

  73. Projahn, M. et al. Contamination of chicken meat with extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Escherichia coli during scalding and defeathering of broiler carcasses. Food Microbiol. 77, 185–191 (2019).

    PubMed  Google Scholar 

  74. Rodrigues, C. et al. Description of Klebsiella africanensis sp. nov., Klebsiella variicola subsp. tropicalensis subsp. nov. and Klebsiella variicola subsp. variicola subsp. nov. Res. Microbiol. 170, 165–170 (2019).

    PubMed  Google Scholar 

  75. Ford, P. & Avison, M. Evolutionary mapping of the SHV β-lactamase and evidence for two separate IS26-dependent bla SHV mobilization events from the Klebsiella pneumoniae chromosome. J. Antimicrob. Chemother. 54, 69–75 (2004).

    CAS  PubMed  Google Scholar 

  76. Liakopoulos, A., Mevius, D. & Ceccarelli, D. A review of SHV extended-spectrum β-lactamases: neglected yet ubiquitous. Front. Microbiol. 5, 1374 (2016).

    Google Scholar 

  77. Turner, M. et al. Plasmid-borne bla SHV genes in Klebsiella pneumoniae are associated with strong promoters. J. Antimicrob. Chemother. 64, 960–964 (2009).

    CAS  PubMed  Google Scholar 

  78. Ito, R. et al. Widespread fosfomycin resistance in Gram-negative bacteria attributable to the chromosomal fosA gene. mBio 8, e00749–e00817 (2017).

    PubMed  PubMed Central  Google Scholar 

  79. Li, J. et al. The nature and epidemiology of OqxAB, a multidrug efflux pump. Antimicrob. Resist. Infect. Control. 8, 44 (2019).

    PubMed  PubMed Central  Google Scholar 

  80. Bernardini, A. et al. The intrinsic resistome of Klebsiella pneumoniae. Int. J. Antimicrob. Agents. 53, 29–33 (2019).

    CAS  PubMed  Google Scholar 

  81. Jana, B. et al. The secondary resistome of multidrug-resistant Klebsiella pneumoniae. Sci. Rep. 7, 42483 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Nicolas-Chanoine, M.-H., Mayer, N., Guyot, K., Dumont, E. & Pagès, J.-M. Interplay between membrane permeability and enzymatic barrier leads to antibiotic-dependent resistance in Klebsiella pneumoniae. Front. Microbiol. 9, 1422 (2018).

    PubMed  PubMed Central  Google Scholar 

  83. Xu, Q. et al. Efflux pumps AcrAB and OqxAB contribute to nitrofurantoin resistance in an uropathogenic Klebsiella pneumoniae isolate. Int. J. Antimicrob. Agents 54, 223–227 (2019).

    CAS  PubMed  Google Scholar 

  84. He, F. et al. Tigecycline susceptibility and the role of efflux pumps in tigecycline resistance in KPC-producing Klebsiella pneumoniae. PLoS one 10, e0119064 (2015).

    PubMed  PubMed Central  Google Scholar 

  85. Fajardo-Lubián, A., Ben Zakour, N. L., Agyekum, A., Qi, Q. & Iredell, J. R. Host adaptation and convergent evolution increases antibiotic resistance without loss of virulence in a major human pathogen. PLoS Pathog. 15, e1007218 (2019). This study shows that deletions or mutations within OmpK35/36 porins are widespread and have emerged in multiple independent lineages of K. pneumoniae, facilitating enhanced resistance to β-lactams (including carbapenems) without significantly reducing the ability to colonize the gut or to cause pneumonia (in murine models).

    PubMed  PubMed Central  Google Scholar 

  86. Wong, J. L. C. et al. OmpK36-mediated carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo. Nat. Commun. 10, 3957 (2019). This study experimentally confirms predictions that specific di-amino acid insertions in OmpK36 constrict its central pore, restricting diffusion of nutrients and carbapenems, and demonstrates using competition assays that these mutations do reduce fitness in the context of the murine pneumonia model.

    PubMed  PubMed Central  Google Scholar 

  87. Lunha, K. et al. High-level carbapenem-resistant OXA-48-producing Klebsiella pneumoniae with a novel OmpK36 variant and low-level, carbapenem-resistant, non-porin-deficient, OXA-181-producing Escherichia coli from Thailand. Diagn. Microbiol. Infect. Dis. 85, 221–226 (2016).

    CAS  PubMed  Google Scholar 

  88. Cain, A. K. et al. Morphological, genomic and transcriptomic responses of Klebsiella pneumoniae to the last-line antibiotic colistin. Sci. Rep. 8, 9868 (2018).

    PubMed  PubMed Central  Google Scholar 

  89. Chang, H.-H. et al. Origin and proliferation of multiple-drug resistance in bacterial pathogens. Microbiol. Mol. Biol. Rev. 79, 101–116 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Lehtinen, S. et al. Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage. Proc. Natl Acad. Sci. USA 114, 1075–1080 (2017).

    CAS  PubMed  Google Scholar 

  91. Conlan, S. et al. Single-molecule sequencing to track plasmid diversity of hospital-associated carbapenemase-producing Enterobacteriaceae. Sci. Transl Med. 6, 254ra126 (2014).

    PubMed  PubMed Central  Google Scholar 

  92. Martin, J. et al. Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long- and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission. J. Antimicrob. Chemother. 72, 3025–3034 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Sheppard, A. E. et al. Nested Russian doll-like genetic mobility drives rapid dissemination of the carbapenem resistance gene bla KPC. Antimicrob. Agents Chemother. 60, 3767–3778 (2016). This study, using a genomic comparison of carbapenem-resistant Enterobacteriaceae isolated from a single health-care institution, highlights the importance of strain, plasmid and transposon transmission for the dissemination of bla KPC carbapenemase genes.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Buckner, M. M. C. et al. Clinically relevant plasmid–host interactions indicate that transcriptional and not genomic modifications ameliorate fitness costs of Klebsiella pneumoniae carbapenemase-carrying plasmids. mBio 9, e02303–e02317 (2018). This study demonstrates that the pKpQIL plasmid of ST258 alters K. pneumoniae gene expression and shows differences in transfer efficiencies of pKpQIL and related plasmids depending on the genetic background of donor and recipient strains.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Hardiman, C. et al. Horizontal transfer of carbapenemase-encoding plasmids and comparison with hospital epidemiological data. Antimicrob. Agents Chemother. 60, 4910–4919 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Lepuschitz, S. et al. Whole genome sequencing reveals resemblance between ESBL-producing and carbapenem resistant Klebsiella pneumoniae isolates from Austrian rivers and clinical isolates from hospitals. Sci. Total. Environ. 662, 227–235 (2019).

    CAS  PubMed  Google Scholar 

  97. Paczosa, M. K. & Mecsas, J. Klebsiella pneumoniae: going on the offense with a strong defense. Microbiol. Mol. Biol. Rev. 80, 629–661 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Bengoechea, J. A. & Sa Pessoa, J. Klebsiella pneumoniae infection biology: living to counteract host defences. FEMS Microbiol. Rev. 43, 123–144 (2019).

    CAS  PubMed  Google Scholar 

  99. Follador, R. et al. The diversity of Klebsiella pneumoniae surface polysaccharides. Microb. Genom. 2, e000073 (2016).

    PubMed  PubMed Central  Google Scholar 

  100. Wyres, K. L. et al. Identification of Klebsiella capsule synthesis loci from whole genome data. Microb. Genom. 2, e000102 (2016).

    PubMed  PubMed Central  Google Scholar 

  101. Bachman, M. A., Lenio, S., Schmidt, L., Oyler, J. E. & Weiser, J. N. Interaction of lipocalin 2, transferrin, and siderophores determines the replicative niche of Klebsiella pneumoniae during pneumonia. mBio 3, e00224-11 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Pan, Y.-J. et al. Genetic analysis of capsular polysaccharide synthesis gene clusters in 79 capsular types of Klebsiella spp. Sci. Rep. 5, 15573 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Whitfield, C. Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu. Rev. Biochem. 75, 39–68 (2006).

    CAS  PubMed  Google Scholar 

  104. Ørskov, I. D. A. & Fife-Asbury, M. A. New Klebsiella capsular antigen, K82, and the deletion of five of those previously assigned. Int. J. Syst. Bacteriol. 27, 386–387 (1977).

    Google Scholar 

  105. Wick, R. R., Heinz, E., Holt, K. E. & Wyres, K. L. Kaptive Web: user-friendly capsule and lipopolysaccharide serotype prediction for Klebsiella genomes. J. Clin. Microbiol. 56, e00197–e00218 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Clarke, B. R. et al. Molecular basis for the structural diversity in serogroup O2-antigen polysaccharides in Klebsiella pneumoniae. J. Biol. Chem. 293, 4666–4679 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Guachalla, L. M. et al. Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3. Sci. Rep. 7, 6635 (2017).

    PubMed  PubMed Central  Google Scholar 

  108. Mostowy, R. J. & Holt, K. E. Diversity-generating machines: genetics of bacterial sugar-coating. Trends Microbiol. 26, 1008–1021 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Khater, F. et al. In silico analysis of usher encoding genes in Klebsiella pneumoniae and characterization of their role in adhesion and colonization. PLoS One 10, e0116215 (2015).

    PubMed  PubMed Central  Google Scholar 

  110. Murphy, C. N., Mortensen, M. S., Krogfelt, K. A. & Clegg, S. Role of Klebsiella pneumoniae type 1 and type 3 fimbriae in colonizing silicone tubes implanted into the bladders of mice as a model of catheter-associated urinary tract infections. Infect. Immun. 81, 3009–3017 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Bachman, M. A. et al. Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2. Infect. Immun. 79, 3309–3316 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Russo, T. A., Olson, R., Macdonald, U., Beanan, J. & Davidson, B. A. Aerobactin, but not yersiniabactin, salmochelin, or enterobactin, enables the growth/survival of hypervirulent (hypermucoviscous) Klebsiella pneumoniae ex vivo and in vivo. Infect. Immun. 83, 3325–3333 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Russo, T. A. et al. Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae. Infect. Immun. 82, 2356–2367 (2014).

    PubMed  PubMed Central  Google Scholar 

  114. Fischbach, M. A. et al. The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2. Proc. Natl Acad. Sci. USA 103, 16502–16507 (2006).

    CAS  PubMed  Google Scholar 

  115. Lam, M. M. C. et al. Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICE Kp in Klebsiella pneumoniae populations. Microb. Genom. https://doi.org/10.1099/mgen.0.000196 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Lam, M. C. C. et al. Tracking key virulence loci encoding aerobactin and salmochelin siderophore synthesis in Klebsiella pneumoniae. Genome Med. 10, 77 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Holden, V. I., Bachman, M. A. & Holden, V. I. Diverging roles of bacterial siderophores during infection. Metallomics 7, 986–995 (2015).

    CAS  PubMed  Google Scholar 

  118. Saha, P. et al. The bacterial siderophore enterobactin confers survival advantage to Salmonella in macrophages. Gut Microbes 10, 412–423 (2019).

    CAS  PubMed  Google Scholar 

  119. Achard, M. E. S. et al. An antioxidant role for catecholate siderophores in Salmonella. Biochem. J. 454, 543–549 (2013).

    CAS  PubMed  Google Scholar 

  120. Holden, V. I., Breen, P., Houle, S., Dozois, C. M. & Bachman, M. A. Klebsiella pneumoniae siderophores induce inflammation, bacterial dissemination, and HIF-1α stablization during pneumonia. mBio 7, e01397–e01416 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Lin, T.-L., Lee, C.-Z., Hsieh, P.-F., Tsai, S.-F. & Wang, J.-T. Characterization of integrative and conjugative element ICEKp1-associated genomic heterogeneity in a Klebsiella pneumoniae strain isolated from a primary liver abscess. J. Bacteriol. 190, 515–526 (2008).

    CAS  PubMed  Google Scholar 

  122. Nassif, X., Fournier, J., Arondel, J. & Sansonetti, P. J. Mucoid phenotype of Klebsiella pneumoniae is a plasmid-encoded virulence factor. Infect. Immun. 57, 546–552 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Yang, X., Wai-Chi Chan, E., Zhang, R. & Chen, S. A conjugative plasmid that augments virulence in Klebsiella pneumoniae. Nat. Microbiol. 4, 2039–2043 (2019).

    PubMed  Google Scholar 

  124. Nougayrède, J. P. et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313, 848–851 (2006).

    PubMed  Google Scholar 

  125. Lai, Y. C. et al. Genotoxic Klebsiella pneumoniae in Taiwan. PLoS One 9, e96292 (2014).

    PubMed  PubMed Central  Google Scholar 

  126. Lu, M.-C. et al. Colibactin contributes to the hypervirulence of pks + K1 CC23 Klebsiella pneumoniae in mouse meningitis infections. Front. Cell. Infect. Microbiol. 7, 1–14 (2017).

    Google Scholar 

  127. Wacharotayankun, R. et al. Enhancement of extracapsular polysaccharide synthesis in Klebsiella pneumoniae by RmpA2, which shows homology to NtrC and FixJ. Infect. Immun. 61, 3164–3174 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Arakawa, Y. et al. Biosynthesis of Klebsiella K2 capsular polysaccharide in Escherichia coli HB101 requires the functions of rmpA and the chromosomal cps gene cluster of the virulent strain Klebsiella pneumoniae Chedid (O1:K2). Infect. Immun. 59, 2043–2050 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Walker, K. A. et al. A Klebsiella pneumoniae regulatory mutant has reduced capsule expression but retains hypermucoviscosity. mBio 10, e00089–e00119 (2019). This study teases apart the roles of rmpA and a newly identified gene immediately downstream of it (rmpC) in hypermucoidy and capsule production.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Wu, C. C., Huang, Y. J., Fung, C. P. & Peng, H. L. Regulation of the Klebsiella pneumoniae Kpc fimbriae by the site-specific recombinase KpcI. Microbiology 156, 1983–1992 (2010).

    CAS  PubMed  Google Scholar 

  131. Earle, S. G. et al. Identifying lineage effects when controlling for population structure improves power in bacterial association studies. Nat. Microbiol. 1, 16041 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Martin, R. M. et al. Identification of pathogenicity-associated loci in Klebsiella pneumoniae from hospitalized patients. mSystems 3, e00015–e00018 (2018). This genome-wide association study tests for K. pneumoniae genes associated with clinical isolates (bacteraemia or pneumonia) versus asymptomatic gut-colonizing isolates and demonstrates independent effects of the tellurite resistance operon ter and a psicose utilization locus.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Russo, T. A. et al. Identification of biomarkers for differentiation of hypervirulent Klebsiella pneumoniae from classical K. pneumoniae. J. Clin. Microbiol. 56, e00776-18 (2018). This study is the first systematic exploration of virulence markers and their relative effect on prediction of the hypervirulence phenotype, highlighting the importance of the aerobactin synthesis locus iuc and other plasmid co-located loci.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Liu, C. & Guo, J. Hypervirulent Klebsiella pneumoniae (hypermucoviscous and aerobactin positive) infection over 6 years in the elderly in China: antimicrobial resistance patterns, molecular epidemiology and risk factor. Ann. Clin. Microbiol. Antimicrob. 18, 4 (2019).

    PubMed  PubMed Central  Google Scholar 

  135. Ye, M. et al. Clinical and genomic analysis of liver abscess-causing Klebsiella pneumoniae identifies new liver abscess-associated virulence genes. Front. Cell Infect. Microbiol. 6, 1–12 (2016).

    Google Scholar 

  136. Wu, K. M. et al. Genome sequencing and comparative analysis of Klebsiella pneumoniae NTUH-K2044, a strain causing liver abscess and meningitis. J. Bacteriol. 191, 4492–4501 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Chen, Y., Chang, H., Lai, Y., Pan, C. & Tsai, S. Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43. Gene 337, 189–198 (2004).

    CAS  PubMed  Google Scholar 

  138. Lery, L. M. et al. Comparative analysis of Klebsiella pneumoniae genomes identifies a phospholipase D family protein as a novel virulence factor. BMC Biol. 12, 41 (2014).

    PubMed  PubMed Central  Google Scholar 

  139. Tu, Y. C. et al. Genetic requirements for Klebsiella pneumoniae-induced liver abscess in an oral infection model. Infect. Immun. 77, 2657–2671 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Bulger, J., MacDonald, U., Olson, R., Beanan, J. & Russo, T. A. Metabolite transporter PEG344 is required for full virulence of hypervirulent Klebsiella pneumoniae strain hvKP1 after pulmonary but not subcutaneous challenge. Infect. Immun. 85, e00093-17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Xie, Y. et al. Emergence of the third-generation cephalosporin-resistant hypervirulent Klebsiella pneumoniae due to the acquisition of a self-transferable bla DHA-1-carrying plasmid by an ST23 strain. Virulence 9, 838–844 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Surgers, L., Boyd, A., Girard, P. M., Arlet, G. & Decré, D. ESBL-producing strain of hypervirulent Klebsiella pneumoniae K2, France. Emerg. Infect. Dis. 22, 1687–1688 (2016).

    PubMed  PubMed Central  Google Scholar 

  143. Shen, D. et al. Emergence of a multidrug-resistant hypervirulent Klebsiella pneumoniae of ST23 with a rare bla CTX-M-24-harboring virulence plasmid. Antimicrob. Agents Chemother. 63, e02273–e02318 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Dong, N., Lin, D., Zhang, R., Chan, E. W. C. & Chen, S. Carriage of bla KPC-2 by a virulence plasmid in hypervirulent Klebsiella pneumoniae. J. Antimicrob. Chemother. 73, 3317–3321 (2018).

    CAS  PubMed  Google Scholar 

  145. Dong, N. et al. Genome analysis of clinical multilocus sequence Type 11 Klebsiella pneumoniae from China. Microb. Genomics 4, https://doi.org/10.1099/mgen.0.000149 (2018).

  146. Weingarten, R. A. et al. Genomic analysis of hospital plumbing reveals diverse reservoir of bacterial plasmids conferring carbapenem resistance. mBio 9, e02011–e02017 (2018).

    PubMed  PubMed Central  Google Scholar 

  147. Sherry, N. L. et al. Genomics for molecular epidemiology and detecting transmission of carbapenemase-producing Enterobacterales in Victoria, Australia, 2012–2016. J. Clin. Microbiol. 57, e00573-19 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Brisse, S. & Verhoef, J. Phylogenetic diversity of Klebsiella pneumoniae and Klebsiella oxytoca clinical isolates revealed by randomly amplified polymorphic DNA, gyrA and parC genes sequencing and automated ribotyping. Int. J. Syst. Evol. Microbiol. 51, 915–924 (2001).

    CAS  PubMed  Google Scholar 

  149. Brisse, S., Passet, V. & Grimont, P. A. D. Description of Klebsiella quasipneumoniae sp., isolated from human infections, with two subspecies, Klebsiella quasipneumoniae subsp. quasipneumoniae subsp. nov. and Klebsiella quasipneumoniae subsp. similipneumoniae subsp. nov., and. demonstration that Klebsiella singaporensis is a junior heterotypic synonym of Klebsiella variicola. Int. J. Syst. Evol. Microbiol. 64, 3146–3152 (2014).

    PubMed  Google Scholar 

  150. Rosenblueth, M., Martínez, L., Silva, J. & Martínez-Romero, E. Klebsiella variicola, a novel species with clinical and plant-associated isolates. Syst. Appl. Microbiol. 27, 27–35 (2004).

    CAS  PubMed  Google Scholar 

  151. Long, S. W. et al. Whole-genome sequencing of a human clinical isolate of the novel species Klebsiella quasivariicola sp. nov. Genome Announc. 5, e01057-17 (2017).

    PubMed  PubMed Central  Google Scholar 

  152. Blin, C., Passet, V., Touchon, M., Rocha, E. P. C. & Brisse, S. Metabolic diversity of the emerging pathogenic lineages of Klebsiella pneumoniae. Env. Microbiol. 19, 1881–1898 (2017). This study is the first exploration of metabolic variation among diverse K. pneumoniae lineages and other members of the species complex, showing that metabolic capabilities — in particular, carbon substrate utilization — can vary substantially between strains.

    CAS  Google Scholar 

  153. Potter, R. F. et al. Population structure, antibiotic resistance, and uropathogenicity of Klebsiella variicola. mBio 9, e02481-18 (2018).

    PubMed  PubMed Central  Google Scholar 

  154. Mathers, A. J. et al. Klebsiella quasipneumoniae provides a window into carbapenemase gene transfer, plasmid rearrangements, and patient interactions with the hospital environment. Antimicrob. Agents Chemother. 63, e02513–e02518 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Brinkac, L. M. et al. Emergence of New Delhi metallo-β-lactamase (NDM-5) in Klebsiella quasipneumoniae from neonates in a Nigerian hospital. mSphere 4, e00685-18 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Rodríguez-Medina, N., Barrios-Camacho, H., Duran-Bedolla, J. & Garza-Ramos, U. Klebsiella variicola: an emerging pathogen in humans. Emerg. Microbes Infect. 8, 973–988 (2019).

    PubMed  PubMed Central  Google Scholar 

  157. Breurec, S. et al. Liver abscess caused by infection with community-acquired Klebsiella quasipneumoniae subsp. quasipneumoniae. Emerg. Infect. Dis. 22, 529–531 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Brisse, S. & Van Duijkeren, E. Identification and antimicrobial susceptibility of 100 Klebsiella animal clinical isolates. Vet. Mirobiol. 105, 307–312 (2005).

    CAS  Google Scholar 

  159. Martínez-Romero, E. et al. Genome misclassification of Klebsiella variicola and Klebsiella quasipneumoniae isolated from plants, animals and humans. Salud Publica. Mex. 60, 52–62 (2018).

    Google Scholar 

  160. Ramirez, M. S., Iriarte, A., Reyes-Lamothe, R., Sherratt, D. J. & Tolmasky, M. E. Small Klebsiella pneumoniae plasmids: neglected contributors to antibiotic resistance. Front. Microbiol. 10, 2182 (2019).

    PubMed  PubMed Central  Google Scholar 

  161. Carattoli, A. et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob. Agents Chemother. 58, 3895–3903 (2014).

    PubMed  PubMed Central  Google Scholar 

  162. Robertson, J. & Nash, J. H. E. MOB-suite: software tools for clustering, reconstruction and typing of plasmids from draft assemblies. Microb. Genom. 4, https://doi.org/10.1099/mgen.0.000206 (2018).

  163. Orlek, A. et al. Ordering the mob: insights into replicon and MOB typing schemes from analysis of a curated dataset of publicly available plasmids. Plasmid 91, 42–52 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Arredondo-Alonso, S., Willems, R. J., van Schaik, W. & Schürch, A. C. On the (im)possibility of reconstructing plasmids from whole-genome short-read sequencing data. Microb. Genom. 3, e000128 (2017).

    PubMed  PubMed Central  Google Scholar 

  165. De Maio, N. et al. Comparison of long-read sequencing technologies in the hybrid assembly of complex bacterial genomes. Microb. Genom. https://doi.org/10.1099/mgen.0.000294 (2019).

  166. Villa, L. et al. Diversity, virulence and antimicrobial resistance of the KPC-producing Klebsiella pneumoniae ST307 clone. Microb. Genom. https://doi.org/10.1099/mgen.0.000110 (2017).

  167. Yeh, K.-M. et al. Revisiting the importance of virulence determinant magA and its surrounding genes in Klebsiella pneumoniae causing pyogenic liver abscesses: exact role in serotype K1 capsule formation. J. Infect. Dis. 201, 1259–1267 (2010).

    CAS  PubMed  Google Scholar 

  168. Yu, W.-L., Lee, M.-F., Tang, H.-J., Chang, M.-C. & Chuang, Y.-C. Low prevalence of rmpA and high tendency of rmpA mutation correspond to low virulence of extended spectrum β-lactamase-producing Klebsiella pneumoniae isolates. Virulence 6, 162–172 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  169. Martinez, J., Martinez, L., Rosenblueth, M., Silva, J. & Martinez-Romero, E. How are gene sequence analyses modifying bacterial taxonomy? The case of Klebsiella. Int. Microbiol. 7, 261–268 (2004).

    CAS  PubMed  Google Scholar 

  170. Ejaz, H. et al. Phylogenetic analysis of Klebsiella pneumoniae from hospitalized children, Pakistan. Emerg. Infect. Dis. 23, 1872–1875 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Cerqueira, G. C. et al. Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks. Proc. Natl Acad. Sci. USA 114, 1135–1140 (2017).

    CAS  PubMed  Google Scholar 

  172. Moradigaravand, D., Martin, V., Peacock, S. J. & Parkhill, J. Evolution and epidemiology of multidrug-resistant Klebsiella pneumoniae in the United Kingdom. mBio 8, e01976-16 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Liu, L. et al. Carbapenem-resistant isolates of the Klebsiella pneumoniae complex in western China: the common ST11 and the surprising hospital-specific types. Clin. Infect. Dis. 67 S263–S265 (2018).

    CAS  PubMed  Google Scholar 

  174. Ocampo, A. M. et al. A two-year surveillance in five Colombian tertiary care hospitals reveals high frequency of non-CG258 clones of carbapenem-resistant Klebsiella pneumoniae with distinct clinical characteristics. Antimicrob. Agents Chemother. 60, 332–342 (2015).

    PubMed  PubMed Central  Google Scholar 

  175. Andrade, L. N. et al. Virulence genes, capsular and plasmid types of multidrug-resistant CTX-M(-2, -8, -15) and KPC-2-producing Klebsiella pneumoniae isolates from four major hospitals in Brazil. Diagn. Microbiol. Infect. Dis. 91, 164–168 (2018).

    CAS  PubMed  Google Scholar 

  176. Deleo, F. R. et al. Molecular dissection of the evolution of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae. Proc. Natl Acad. Sci. USA 111, 4988–4993 (2014).

    CAS  PubMed  Google Scholar 

  177. Lowe, M. et al. Klebsiella pneumoniae ST307 with bla OXA-181, South Africa, 2014–2016. Emerg. Infect. Dis. 25, 739–747 (2019).

    PubMed  PubMed Central  Google Scholar 

  178. Chung The, H. et al. A high-resolution genomic analysis of multidrug-resistant hospital outbreaks of Klebsiella pneumoniae. EMBO Mol. Med. 7, 227–239 (2015).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are supported by Monash University and the Viertel Foundation of Australia. The authors thank Ryan Wick for assistance in creating the phylogenetic tree shown in Fig. 1.

Author information

Authors and Affiliations

Authors

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Kathryn E. Holt.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Microbiology thanks J. Pitout, T. Russo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

BIGSdb: https://bigsdb.pasteur.fr/klebsiella/klebsiella.html

Kleborate: https://github.com/katholt/Kleborate

PathogenWatch: https://pathogen.watch/

Supplementary information

Glossary

Disability-adjusted life years

A measure of disease burden estimated as the number of years lost to ill-health, disability and/or death.

Problem clones

Klebsiella pneumoniae clones that are over-represented among human infection isolates.

Endophthalmitis

Inflammation of the eye, usually caused by bacterial or fungal infection.

Necrotizing fasciitis

An infection resulting in rapid death of the skin and soft tissues.

Hypervirulent

A term used to describe a clinical phenomenon of severe community-acquired Klebsiella pneumoniae disease, which is typically associated with the presence of a combination of multiple acquired virulence loci.

Core genes

Genes that are present in all members of a given species (or nearly all, typically ≥95%).

Accessory genes

Genes that are present in some members of a given species but not all (typically <95%).

Core-genome multilocus sequence typing

(cgMLST). A classification scheme and nomenclature based on nucleotide sequence variation in core genes (usually hundreds of genes).

Clones

A generic term used to describe subpopulations of Klebsiella pneumoniae strains with a recent common ancestor identified through allelic variation in core genes, either by multilocus sequence typing or core-genome multilocus sequence typing (specifically called ‘clonal groups’ or ‘CGs’) or by core-genome phylogenetics (specifically called ‘lineages’).

Integrative conjugative elements

(ICEs). Mobile pieces of DNA that encode the machinery required for their own integration and excision from the bacterial host chromosome and transfer between bacterial cells.

ESKAPE pathogens

The six most common causes of multidrug-resistant health-care-associated infection defined by the Infectious Diseases Society of America: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species.

Simpson diversity

A measure of diversity that considers the total number of distinct entities (species, sequence types and so on) as well as their relative abundance.

Minimum inhibitory concentration

(MIC). The lowest concentration of a compound (usually an antibiotic) that is able to inhibit growth of a given bacterial isolate.

Pathogenicity factors

Features encoded by loci that are present in all Klebsiella pneumoniae (although there may be important allelic variants) and required for ‘classical’ opportunistic infections.

K-locus

The capsule (K antigen) biosynthesis locus.

Rhinoscleromatis

A rare chronic infection characterized by granulomas (structure formed from a collection of white blood cells) in the upper airways.

O-loci

The outer lipopolysaccharide (O antigen) biosynthesis loci.

Virulence factors

Features encoded by accessory loci which are entirely absent from most Klebsiella pneumoniae but whose presence increases either disease severity or propensity to cause disease.

FIBK replicons

Plasmids of incompatibility type IncFIBK.

Hypermucoidy

A phenotypic state characterized by ‘sticky’ growth and identified by production of a viscous filament (≥5 mm) when a colony is stretched by a culture loop.

Psicose sugar

A monosaccharide molecule, also known as allulose.

Classical infections

A term used to refer to opportunistic healthcare-associated Klebsiella pneumoniae infections.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wyres, K.L., Lam, M.M.C. & Holt, K.E. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol 18, 344–359 (2020). https://doi.org/10.1038/s41579-019-0315-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41579-019-0315-1

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing