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Abstract

The outer polysaccharide capsule and lipopolysaccharide (LPS) antigens are key targets for novel control strategies targeting and related taxa from the species complex (KpSC), including vaccines, phage and monoclonal antibody therapies. Given the importance and growing interest in these highly diverse surface antigens, we had previously developed Kaptive, a tool for rapidly identifying and typing capsule (K) and outer LPS (O) loci from whole genome sequence data. Here, we report two significant updates, now freely available in Kaptive 2.0 (https://github.com/katholt/kaptive): (i) the addition of 16 novel K locus sequences to the K locus reference database following an extensive search of >17 000 KpSC genomes; and (ii) enhanced O locus typing to enable prediction of the clinically relevant O2 antigen (sub)types, for which the genetic determinants have been recently described. We applied Kaptive 2.0 to a curated dataset of >12 000 public KpSC genomes to explore for the first time, to the best of our knowledge, the distribution of predicted O (sub)types across species, sampling niches and clones, which highlighted key differences in the distributions that warrant further investigation. As the uptake of genomic surveillance approaches continues to expand globally, the application of Kaptive 2.0 will generate novel insights essential for the design of effective KpSC control strategies.

Funding
This study was supported by the:
  • National Health and Medical Research Council (Award APP1176192)
    • Principle Award Recipient: KellyL. Wyres
  • Bill and Melinda Gates Foundation (Award INV023041)
    • Principle Award Recipient: KathrynE. Holt
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-03-21
2022-07-06
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References

  1. Wyres KL, Lam MMC, Holt KE. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol 2020; 18:344–359 [View Article] [PubMed]
    [Google Scholar]
  2. Pendleton JN, Gorman SP, Gilmore BF. Clinical relevance of the ESKAPE pathogens. Expert Rev Anti Infect Ther 2013; 11:297–308 [View Article] [PubMed]
    [Google Scholar]
  3. Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha 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 2019; 19:56–66 [View Article] [PubMed]
    [Google Scholar]
  4. Okomo U, Akpalu ENK, Le Doare K, Roca A, Cousens S 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 2019; 19:1219–1234 [View Article] [PubMed]
    [Google Scholar]
  5. Sands K, Carvalho MJ, Portal E, Thomson K, Dyer C et al. Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries. Nat Microbiol 2021; 6:512–523 [View Article] [PubMed]
    [Google Scholar]
  6. World Health Organization Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery, and Devlopment of New Antibiotics Geneva: World Health Organization; 2017
    [Google Scholar]
  7. Motley MP, Fries BC. A new take on an old remedy: generating antibodies against multidrug-resistant gram-negative bacteria in a postantibiotic world. mSphere 2017; 2:e00397-17 [View Article] [PubMed]
    [Google Scholar]
  8. Aleshkin AV, Ershova ON, Volozhantsev NV, Svetoch EA, Popova AV et al. Phagebiotics in treatment and prophylaxis of healthcare-associated infections. Bacteriophage 2016; 6:e1251379 [View Article] [PubMed]
    [Google Scholar]
  9. Assoni L, Girardello R, Converso TR, Darrieux M. Current stage in the development of Klebsiella pneumoniae vaccines. Infect Dis Ther 2021; 10:2157–2175 [View Article] [PubMed]
    [Google Scholar]
  10. Cortés G, Borrell N, de Astorza B, Gómez C, Sauleda J et al. Molecular analysis of the contribution of the capsular polysaccharide and the lipopolysaccharide O side chain to the virulence of Klebsiella pneumoniae in a murine model of pneumonia. Infect Immun 2002; 70:2583–2590 [View Article] [PubMed]
    [Google Scholar]
  11. Lawlor MS, Hsu J, Rick PD, Miller VL. Identification of Klebsiella pneumoniae virulence determinants using an intranasal infection model. Mol Microbiol 2005; 58:1054–1073 [View Article] [PubMed]
    [Google Scholar]
  12. Evrard B, Balestrino D, Dosgilbert A, Bouya-Gachancard J-LJ, Charbonnel N et al. Roles of capsule and lipopolysaccharide O antigen in interactions of human monocyte-derived dendritic cells and Klebsiella pneumoniae. Infect Immun 2010; 78:210–219 [View Article] [PubMed]
    [Google Scholar]
  13. March C, Cano V, Moranta D, Llobet E, Pérez-Gutiérrez C et al. Role of bacterial surface structures on the interaction of Klebsiella pneumoniae with phagocytes. PLoS One 2013; 8:e56847 [View Article] [PubMed]
    [Google Scholar]
  14. D’Andrea MM, Marmo P, Henrici De Angelis L, Palmieri M, Ciacci N et al. φBO1E, a newly discovered lytic bacteriophage targeting carbapenemase-producing Klebsiella pneumoniae of the pandemic clonal group 258 clade II lineage. Sci Rep 2017; 7:2614 [View Article] [PubMed]
    [Google Scholar]
  15. Szijártó V, Guachalla LM, Hartl K, Varga C, Banerjee P et al. Both clades of the epidemic KPC-producing Klebsiella pneumoniae clone ST258 share a modified galactan O-antigen type. Int J Med Microbiol 2016; 306:89–98 [View Article] [PubMed]
    [Google Scholar]
  16. Guachalla LM, Stojkovic K, Hartl K, Kaszowska M, Kumar Y et al. Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3. Sci Rep 2017; 7:6635 [View Article] [PubMed]
    [Google Scholar]
  17. Pennini ME, De Marco A, Pelletier M, Bonnell J, Cvitkovic R et al. Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae. Nat Commun 2017; 8:1991 [View Article] [PubMed]
    [Google Scholar]
  18. Seeberger PH, Pereira CL, Khan N, Xiao G, Diago-Navarro E et al. A semi-synthetic glycoconjugate vaccine candidate for carbapenem-resistant Klebsiella pneumoniae. Angew Chem Int Ed Engl 2017; 56:13973–13978 [View Article] [PubMed]
    [Google Scholar]
  19. Ravinder M, Liao K-S, Cheng Y-Y, Pawar S, Lin T-L et al. A synthetic carbohydrate-protein conjugate vaccine candidate against Klebsiella pneumoniae serotype K2. J Org Chem 2020; 85:15964–15997 [View Article] [PubMed]
    [Google Scholar]
  20. Feldman MF, Mayer Bridwell AE, Scott NE, Vinogradov E, McKee SR et al. A promising bioconjugate vaccine against hypervirulent Klebsiella pneumoniae. Proc Natl Acad Sci USA 2019; 116:18655–18663 [View Article] [PubMed]
    [Google Scholar]
  21. Campbell WN, Hendrix E, Cryz S, Cross AS. Immunogenicity of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered to victims of acute trauma. Clin Infect Dis 1996; 23:179–181 [View Article] [PubMed]
    [Google Scholar]
  22. Hegerle N, Choi M, Sinclair J, Amin MN, Ollivault-Shiflett M et al. Development of a broad spectrum glycoconjugate vaccine to prevent wound and disseminated infections with Klebsiella pneumoniae and Pseudomonas aeruginosa. PLoS One 2018; 13:e0203143 [View Article] [PubMed]
    [Google Scholar]
  23. Alaimo C, Haffner S. Safety and Immunogenicity of a Klebsiella pneumoniae Tetravalent Bioconjugate Vaccine (Kleb4v), identifier NCT04959344; 2021 https://clinicaltrials.gov/
  24. Edmunds PN. Further Klebsiella capsule types. J Infect Dis 1954; 94:65–71 [View Article] [PubMed]
    [Google Scholar]
  25. Edwards PR, Fife MA. Capsule types of Klebsiella. J Infect Dis 1952; 91:92–104 [View Article] [PubMed]
    [Google Scholar]
  26. Orskov I, Fife-Asbury MA. New Klebsiella capsular antigen, K82, and the deletion of five of those previously assigned. Int J Syst Bacteriol 1977; 27:386–387 [View Article]
    [Google Scholar]
  27. Trautmann M, Ruhnke M, Rukavina T, Held TK, Cross AS et al. O-antigen seroepidemiology of Klebsiella clinical isolates and implications for immunoprophylaxis of Klebsiella infections. Clin Diagn Lab Immunol 1997; 4:550–555 [View Article]
    [Google Scholar]
  28. Follador R, Heinz E, Wyres KL, Ellington MJ, Kowarik M et al. The diversity of Klebsiella pneumoniae surface polysaccharides. Microb Genom 2016; 2:e000073 [View Article] [PubMed]
    [Google Scholar]
  29. 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:e000102 [View Article] [PubMed]
    [Google Scholar]
  30. Wick RR, Heinz E, Holt KE, Wyres KL. Kaptive web: user-friendly capsule and lipopolysaccharide serotype prediction for Klebsiella genomes. J Clin Microbiol 2018; 56:e00197-18 [View Article] [PubMed]
    [Google Scholar]
  31. Whitfield C. Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu Rev Biochem 2006; 75:39–68 [View Article] [PubMed]
    [Google Scholar]
  32. Pan Y-J, Lin T-L, Chen C-T, Chen Y-Y, Hsieh P-F et al. Genetic analysis of capsular polysaccharide synthesis gene clusters in 79 capsular types of Klebsiella spp. Sci Rep 2015; 5:15573 [View Article] [PubMed]
    [Google Scholar]
  33. Cuthbertson L, Kimber MS, Whitfield C. Substrate binding by a bacterial ABC transporter involved in polysaccharide export. Proc Natl Acad Sci USA 2007; 104:19529–19534 [View Article] [PubMed]
    [Google Scholar]
  34. Cryz SJ, Mortimer PM, Mansfield V, Germanier R. Seroepidemiology of Klebsiella bacteremic isolates and implications for vaccine development. J Clin Microbiol 1986; 23:687–690 [View Article] [PubMed]
    [Google Scholar]
  35. Tsay R-W, Siu LK, Fung C-P, Chang F-Y. Characteristics of bacteremia between community-acquired and nosocomial Klebsiella pneumoniae infection. Arch Intern Med 2002; 162:1021 [View Article] [PubMed]
    [Google Scholar]
  36. Jenney AW, Clements A, Farn JL, Wijburg OL, McGlinchey A et al. Seroepidemiology of Klebsiella pneumoniae in an Australian tertiary hospital and its implications for vaccine development. J Clin Microbiol 2006; 44:102–107 [View Article] [PubMed]
    [Google Scholar]
  37. 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] [PubMed]
    [Google Scholar]
  38. Lam MMC, Wick RR, Watts SC, Cerdeira LT, Wyres KL et al. A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex. Nat Commun 2021; 12:4188 [View Article] [PubMed]
    [Google Scholar]
  39. Fang C-T, Shih Y-J, Cheong C-M, Yi W-C. Rapid and accurate determination of lipopolysaccharide O-antigen types in Klebsiella pneumoniae with a novel PCR-based O-genotyping method. J Clin Microbiol 2016; 54:666–675 [View Article] [PubMed]
    [Google Scholar]
  40. Whitfield C, Richards JC, Perry MB, Clarke BR, MacLean LL. Expression of two structurally distinct D-galactan O antigens in the lipopolysaccharide of Klebsiella pneumoniae serotype O1. J Bacteriol 1991; 173:1420–1431 [View Article] [PubMed]
    [Google Scholar]
  41. Clarke BR, Whitfield C. Molecular cloning of the rfb region of Klebsiella pneumoniae serotype O1:K20: the rfb gene cluster is responsible for synthesis of the D-galactan I O polysaccharide. J Bacteriol 1992; 174:4614–4621 [View Article] [PubMed]
    [Google Scholar]
  42. Sugiyama T, Kido N, Kato Y, Koide N, Yoshida T et al. Evolutionary relationship among rfb gene clusters synthesizing mannose homopolymer as O-specific polysaccharides in Escherichia coli and Klebsiella. Gene 1997; 198:111–113 [View Article] [PubMed]
    [Google Scholar]
  43. Kelly RF, Perry MB, MacLean LL, Whitfield C. Structures of the O-antigens of Klebsiella serotypes 02 (2a,2e), 02 (2a,2e,2h), and 02 (2a,2f,2g), members of a family of related D-galactan O-antigens in Klebsiella spp. J Endotoxin Res 2016; 2:131–140 [View Article]
    [Google Scholar]
  44. Hsieh P-F, Wu M-C, Yang F-L, Chen C-T, Lou T-C et al. D-galactan II is an immunodominant antigen in O1 lipopolysaccharide and affects virulence in Klebsiella pneumoniae: implication in vaccine design. Front Microbiol 2014; 5:608 [View Article] [PubMed]
    [Google Scholar]
  45. Kelly SD, Clarke BR, Ovchinnikova OG, Sweeney RP, Williamson ML et al. Klebsiella pneumoniae O1 and O2ac antigens provide prototypes for an unusual strategy for polysaccharide antigen diversification. J Biol Chem 2019; 294:10863–10876 [View Article] [PubMed]
    [Google Scholar]
  46. Clarke BR, Ovchinnikova OG, Kelly SD, Williamson ML, Butler JE et al. Molecular basis for the structural diversity in serogroup O2-antigen polysaccharides in Klebsiella pneumoniae. J Biol Chem 2018; 293:4666–4679 [View Article] [PubMed]
    [Google Scholar]
  47. Bulati M, Busà R, Carcione C, Iannolo G, Di Mento G et al. Klebsiella pneumoniae lipopolysaccharides serotype O2afg induce poor inflammatory immune responses ex vivo. Microorganisms 2021; 9:1317 [View Article] [PubMed]
    [Google Scholar]
  48. 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]
  49. Fu L, Niu B, Zhu Z, Wu S, Li W. CD-HIT: accelerated for clustering the next-generation sequencing data. Bioinformatics 2012; 28:3150–3152 [View Article] [PubMed]
    [Google Scholar]
  50. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  51. Carver TJ, Rutherford KM, Berriman M, Rajandream M-A, Barrell BG et al. ACT: the Artemis Comparison Tool. Bioinformatics 2005; 21:3422–3423 [View Article] [PubMed]
    [Google Scholar]
  52. Siguier P, Perochon J, Lestrade L, Mahillon J, Chandler M. ISfinder: the reference centre for bacterial insertion sequences. Nucleic Acids Res 2006; 34:D32–D36 [View Article] [PubMed]
    [Google Scholar]
  53. Gilchrist CLM, Chooi Y-H. Clinker & clustermap.js: automatic generation of gene cluster comparison figures. Bioinformatics 2021btab007 [View Article] [PubMed]
    [Google Scholar]
  54. Raffelsberger N, Hetland MAK, Svendsen K, Småbrekke L, Löhr IH et al. Gastrointestinal carriage of Klebsiella pneumoniae in a general adult population: a cross-sectional study of risk factors and bacterial genomic diversity. Gut Microbes 2021; 13:1939599 [View Article] [PubMed]
    [Google Scholar]
  55. Thorpe H, Booton R, Kallonen T, Gibbon MJ, Couto N et al. One health or three? Transmission modelling of Klebsiella isolates reveals ecological barriers to transmission between humans, animals and the environment. bioRxiv 20212021.08.05.455249 [View Article]
    [Google Scholar]
  56. Rahn A, Beis K, Naismith JH, Whitfield C. A novel outer membrane protein, Wzi, is involved in surface assembly of the Escherichia coli K30 group 1 capsule. J Bacteriol 2003; 185:5882–5890 [View Article] [PubMed]
    [Google Scholar]
  57. Holt KE, Lassalle F, Wyres KL, Wick R, Mostowy RJ. Diversity and evolution of surface polysaccharide synthesis loci in Enterobacteriales. ISME J 2020; 14:1713–1730 [View Article] [PubMed]
    [Google Scholar]
  58. Hansen DS, Mestre F, Alberti S, Hernández-Allés S, Alvarez D et al. Klebsiella pneumoniae lipopolysaccharide O typing: revision of prototype strains and O-group distribution among clinical isolates from different sources and countries. J Clin Microbiol 1999; 37:56–62 [View Article] [PubMed]
    [Google Scholar]
  59. Choi M, Hegerle N, Nkeze J, Sen S, Jamindar S et al. The diversity of lipopolysaccharide (O) and capsular polysaccharide (K) antigens of invasive Klebsiella pneumoniae in a multi-country collection. Front Microbiol 2020; 11:1249 [View Article] [PubMed]
    [Google Scholar]
  60. Fostervold A, Hetland MAK, Bakksjø R, Bernhoff E, Holt KE et al. A nationwide genomic study of clinical Klebsiella pneumoniae in Norway 2001-2015: introduction and spread of ESBL facilitated by CG15 and CG307. bioRxiv 20212021.07.16.452602 [View Article]
    [Google Scholar]
  61. Leangapichart T, Lunha K, Jiwakanon J, Angkititrakul S, Järhult JD et al. Characterization of Klebsiella pneumoniae complex isolates from pigs and humans in farms in Thailand: population genomic structure, antibiotic resistance and virulence genes. J Antimicrob Chemother 2021; 76:2012–2016 [View Article] [PubMed]
    [Google Scholar]
  62. Potter RF, Lainhart W, Twentyman J, Wallace MA, Wang B et al. Population structure, antibiotic resistance, and uropathogenicity of Klebsiella variicola. mBio 2018; 9:e02481-18 [View Article] [PubMed]
    [Google Scholar]
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