1887

Abstract

Mobile genetic elements (MGEs) that frequently transfer within and between bacterial species play a critical role in bacterial evolution, and often carry key accessory genes that associate with a bacteria’s ability to cause disease. MGEs carrying antimicrobial resistance (AMR) and/or virulence determinants are common in the opportunistic pathogen Klebsiella pneumoniae, which is a leading cause of highly drug-resistant infections in hospitals. Well-characterised virulence determinants in K. pneumoniae include the polyketide synthesis loci ybt and clb (also known as pks), encoding the iron-scavenging siderophore yersiniabactin and genotoxin colibactin, respectively. These loci are located within an MGE called ICEKp, which is the most common virulence-associated MGE of K. pneumoniae, providing a mechanism for these virulence factors to spread within the population. Here we apply population genomics to investigate the prevalence, evolution and mobility of ybt and clb in K. pneumoniae populations through comparative analysis of 2498 whole-genome sequences. The ybt locus was detected in 40 % of K. pneumoniae genomes, particularly amongst those associated with invasive infections. We identified 17 distinct ybt lineages and 3 clb lineages, each associated with one of 14 different structural variants of ICEKp. Comparison with the wider population of the family Enterobacteriaceae revealed occasional ICEKp acquisition by other members. The clb locus was present in 14 % of all K. pneumoniae and 38.4 % of ybt+ genomes. Hundreds of independent ICEKp integration events were detected affecting hundreds of phylogenetically distinct K. pneumoniae lineages, including at least 19 in the globally-disseminated carbapenem-resistant clone CG258. A novel plasmid-encoded form of ybt was also identified, representing a new mechanism for ybt dispersal in K. pneumoniae populations. These data indicate that MGEs carrying ybt and clb circulate freely in the K. pneumoniae population, including among multidrug-resistant strains, and should be considered a target for genomic surveillance along with AMR determinants.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000196
2018-07-09
2024-03-19
Loading full text...

Full text loading...

/deliver/fulltext/mgen/4/9/mgen000196.html?itemId=/content/journal/mgen/10.1099/mgen.0.000196&mimeType=html&fmt=ahah

References

  1. Frost LS, Leplae R, Summers AO, Toussaint A, Edmonton A. Mobile genetic elements: the agents of open source evolution. Nat Rev Microbiol 2005; 3:722–732 [View Article][PubMed]
    [Google Scholar]
  2. McNally A, Thomson NR, Reuter S, Wren BW. 'Add, stir and reduce': Yersinia spp. as model bacteria for pathogen evolution. Nat Rev Microbiol 2016; 14:177–190 [View Article][PubMed]
    [Google Scholar]
  3. Lin TL, Lee CZ, Hsieh PF, Tsai SF, Wang JT. Characterization of integrative and conjugative element ICEKp1-associated genomic heterogeneity in a Klebsiella pneumoniae strain isolated from a primary liver abscess. J Bacteriol 2008; 190:515–526 [View Article][PubMed]
    [Google Scholar]
  4. Wooldridge KG, Williams PH. Iron uptake mechanisms of pathogenic bacteria. FEMS Microbiol Rev 1993; 12:325-48[PubMed]
    [Google Scholar]
  5. Koczura R, Kaznowski A. Occurrence of the Yersinia high-pathogenicity island and iron uptake systems in clinical isolates of Klebsiella pneumoniae. Microb Pathog 2003; 35:197–202 [View Article][PubMed]
    [Google Scholar]
  6. Holden VI, Bachman MA. Diverging roles of bacterial siderophores during infection. Metallomics 2015; 7:986–995 [View Article][PubMed]
    [Google Scholar]
  7. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN et al. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 2002; 10:1033–1043 [View Article][PubMed]
    [Google Scholar]
  8. Bachman MA, Miller VL, Weiser JN. Mucosal lipocalin 2 has pro-inflammatory and iron-sequestering effects in response to bacterial enterobactin. PLoS Pathog 2009; 5:e1000622 [View Article][PubMed]
    [Google Scholar]
  9. Bachman MA, Oyler JE, Burns SH, Caza M, Lépine F et al. Klebsiella pneumoniae yersiniabactin promotes respiratory tract infection through evasion of lipocalin 2. Infect Immun 2011; 79:3309–3316 [View Article][PubMed]
    [Google Scholar]
  10. Holden VI, Breen P, Houle S, Dozois CM, Bachman MA. Klebsiella pneumoniae siderophores induce inflammation, bacterial dissemination, and HIF-1α stabilization during Pneumonia. MBio 2016; 7:e01397-16-10 [View Article]
    [Google Scholar]
  11. Lawlor MS, O'Connor C, Miller VL. Yersiniabactin is a virulence factor for Klebsiella pneumoniae during pulmonary infection. Infect Immun 2007; 75:1463–1472 [View Article][PubMed]
    [Google Scholar]
  12. Koh EI, Henderson JP. Microbial copper-binding siderophores at the host–pathogen interface. J Biol Chem 2015; 290:18967–18974 [View Article][PubMed]
    [Google Scholar]
  13. 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]
  14. Abergel RJ, Moore EG, Strong RK, Raymond KN. Microbial evasion of the immune system: structural modifications of enterobactin impair siderocalin recognition. J Am Chem Soc 2006; 128:10998–10999 [View Article][PubMed]
    [Google Scholar]
  15. Konopka K, Bindereif A, Neilands JB. Aerobactin-mediated utilization of transferrin iron. Biochemistry 1982; 21:6503–6508 [View Article][PubMed]
    [Google Scholar]
  16. Bach S, de Almeida A, Carniel E. The Yersinia high-pathogenicity island is present in different members of the family Enterobacteriaceae. FEMS Microbiol Lett 2000; 183:289–294 [View Article][PubMed]
    [Google Scholar]
  17. Lai YC, Lin AC, Chiang MK, Dai YH, Hsu CC et al. Genotoxic Klebsiella pneumoniae in Taiwan. PLoS One 2014; 9:e96292 [View Article][PubMed]
    [Google Scholar]
  18. Lery LM, Frangeul L, Tomas A, Passet V, Almeida AS et al. Comparative analysis of Klebsiella pneumoniae genomes identifies a phospholipase D family protein as a novel virulence factor. BMC Biol 2014; 12:41 [View Article][PubMed]
    [Google Scholar]
  19. Marcoleta AE, Berríos-Pastén C, Nuñez G, Monasterio O, Lagos R. Klebsiella pneumoniae asparagine tDNAs are integration hotspots for different genomic islands encoding microcin E492 production determinants and other putative virulence factors present in hypervirulent strains. Front Microbiol 2016; 7:1–17 [View Article][PubMed]
    [Google Scholar]
  20. Putze J, Hennequin C, Nougayrède JP, Zhang W, Homburg S, Karch H et al. Genetic structure and distribution of the colibactin genomic island among members of the family Enterobacteriaceae. Infect Immun 2009; 77:4696–4703 [View Article][PubMed]
    [Google Scholar]
  21. Vizcaino MI, Crawford JM. The colibactin warhead crosslinks DNA. Nat Chem 2015; 7:411–417 [View Article][PubMed]
    [Google Scholar]
  22. Carniel E, Mazigh D, Mollaret HH. Expression of iron-regulated proteins in Yersinia species and their relation to virulence. Infect Immun 1987; 55:277–280[PubMed]
    [Google Scholar]
  23. de Almeida AM, Guiyoule A, Guilvout I, Iteman I, Baranton G et al. Chromosomal irp2 gene in Yersinia: distribution, expression, deletion and impact on virulence. Microb Pathog 1993; 14:9–21 [View Article][PubMed]
    [Google Scholar]
  24. Pelludat C, Rakin A, Jacobi CA, Schubert S, Heesemann J. The yersiniabactin biosynthetic gene cluster of Yersinia enterocolitica: organization and siderophore-dependent regulation. J Bacteriol 1998; 180:538–546[PubMed]
    [Google Scholar]
  25. 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]
  26. Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Daikos GL et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis 2013; 13:785–796 [View Article][PubMed]
    [Google Scholar]
  27. Conlan S, Deming C, Tsai YC, Lau AF, Dekker JP et al. Complete genome sequence of a Klebsiella pneumoniae isolate with chromosomally encoded carbapenem resistance and colibactin synthesis loci. Genome Announc 2014; 2:e01332-14 [View Article][PubMed]
    [Google Scholar]
  28. Bowers JR, Kitchel B, Driebe EM, MacCannell DR, Roe C et al. Genomic analysis of the emergence and rapid global dissemination of the clonal group 258 Klebsiella pneumoniae pandemic. PLoS One 2015; 10:e013372724 [View Article][PubMed]
    [Google Scholar]
  29. Paauw A, Leverstein-van Hall MA, Verhoef J, Fluit AC. Evolution in quantum leaps: multiple combinatorial transfers of HPI and other genetic modules in Enterobacteriaceae. PLoS One 2010; 5:e8662 [View Article][PubMed]
    [Google Scholar]
  30. Ch'ng SL, Octavia S, Xia Q, Duong A, Tanaka MM et al. Population structure and evolution of pathogenicity of Yersinia pseudotuberculosis. Appl Environ Microbiol 2011; 77:768–775 [View Article][PubMed]
    [Google Scholar]
  31. Schubert S, Rakin A, Heesemann J. The Yersinia high-pathogenicity island (HPI): evolutionary and functional aspects. Int J Med Microbiol 2004; 294:83–94 [View Article][PubMed]
    [Google Scholar]
  32. Croucher NJ, Campo JJ, Le TQ, Liang X, Bentley SD et al. Diverse evolutionary patterns of pneumococcal antigens identified by pangenome-wide immunological screening. Proc Natl Acad Sci USA 2017; 114:E357E366 [View Article][PubMed]
    [Google Scholar]
  33. Hesse E, O'Brien S, Tromas N, Bayer F, Luján AM et al. Ecological selection of siderophore-producing microbial taxa in response to heavy metal contamination. Ecol Lett 2018; 21: [View Article][PubMed]
    [Google Scholar]
  34. Löhr IH, Hülter N, Bernhoff E, Johnsen PJ, Sundsfjord A et al. Persistence of a pKPN3-like CTX-M-15-encoding IncFIIK plasmid in a Klebsiella pneumoniae ST17 host during two years of intestinal colonization. PLoS One 2015; 10:e0116516 [View Article][PubMed]
    [Google Scholar]
  35. Sandegren L, Linkevicius M, Lytsy B, Melhus Å, Andersson DI. Transfer of an Escherichia coli ST131 multiresistance cassette has created a Klebsiella pneumoniae-specific plasmid associated with a major nosocomial outbreak. J Antimicrob Chemother 2012; 67:74–83 [View Article][PubMed]
    [Google Scholar]
  36. Villa L, García-Fernández A, Fortini D, Carattoli A. Replicon sequence typing of IncF plasmids carrying virulence and resistance determinants. J Antimicrob Chemother 2010; 65:2518–2529 [View Article][PubMed]
    [Google Scholar]
  37. Kwong JC, McCallum N, Sintchenko V, Howden BP. Whole genome sequencing in clinical and public health microbiology. Pathology 2015; 47:199–210 [View Article][PubMed]
    [Google Scholar]
  38. Robilotti E, Kamboj M. Integration of whole-genome sequencing into infection control practices: the potential and the hurdles. J Clin Microbiol 2015; 53:1054–1055 [View Article][PubMed]
    [Google Scholar]
  39. Inouye M, Dashnow H, Raven LA, Schultz MB, Pope BJ et al. SRST2: rapid genomic surveillance for public health and hospital microbiology labs. Genome Med 2014; 6:90 [View Article][PubMed]
    [Google Scholar]
  40. Arnold RS, Thom KA, Sharma S, Phillips M, Kristie Johnson J et al. Emergence of Klebsiella pneumoniae carbapenemase-producing bacteria. South Med J 2011; 104:40–45 [View Article][PubMed]
    [Google Scholar]
  41. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K et al. Characterization of a new metallo-β-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009; 53:5046–5054 [View Article][PubMed]
    [Google Scholar]
  42. Lee IR, Molton JS, Wyres KL, Gorrie C, Wong J et al. Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population. Sci Rep 2016; 6:29316 [View Article][PubMed]
    [Google Scholar]
  43. Wyres KL, Wick RR, Gorrie C, Jenney A, Follador R et al. Identification of Klebsiella capsule synthesis loci from whole genome data. Microb Genom 2016; 2: [View Article][PubMed]
    [Google Scholar]
  44. Gorrie CL, Mirceta M, Wick RR, Edwards DJ, Thomson NR et al. Gastrointestinal carriage is a major reservoir of Klebsiella pneumoniae infection in intensive care patients. Clin Infect Dis 2017; 65:208–215 [View Article][PubMed]
    [Google Scholar]
  45. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article][PubMed]
    [Google Scholar]
  46. 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]
  47. 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]
  48. Maiden MC. Multilocus sequence typing of bacteria. Annu Rev Microbiol 2006; 60:561–588 [View Article][PubMed]
    [Google Scholar]
  49. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015; 43:e15 [View Article][PubMed]
    [Google Scholar]
  50. Stamatakis A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 2006; 22:2688–2690 [View Article][PubMed]
    [Google Scholar]
  51. Deleo FR, Chen L, Porcella SF, Martens CA, Kobayashi SD et al. Molecular dissection of the evolution of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae. Proc Natl Acad Sci USA 2014; 111:4988–4993 [View Article][PubMed]
    [Google Scholar]
  52. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 2013; 30:2725–2729 [View Article][PubMed]
    [Google Scholar]
  53. Wick RR, Schultz MB, Zobel J, Holt KE. Bandage: interactive visualization of de novo genome assemblies. Bioinformatics 2015; 31:3350–3352 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000196
Loading
/content/journal/mgen/10.1099/mgen.0.000196
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF

Supplementary File 2

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error