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Abstract

, a clinically significant pathogen, causes invasive diseases in children and older adults. Pneumococcal conjugate vaccines (PCVs) have substantially reduced the incidence of vaccine serotype (VT) pneumococcal diseases. However, serotype replacement, characterized by the emergence of non-vaccine serotypes (NVTs), presents a persistent challenge to disease prevention. To address this, we analysed 236 pneumococcal isolates collected in South Korea between 1997 and 2023, spanning both pre- and post-PCV13 periods. Whole-genome sequencing was performed to assess serotypes, antimicrobial resistance, virulence factors and global pneumococcal sequence clusters (GPSCs). Capsular switching events and the relationships among pneumococcal lineages, serotypes and disease invasiveness were also evaluated. Among the 37 identified serotypes, NVTs such as 23A, 15B/15C and 10A were dominant post-PCV13. Serotype 10A, associated with invasive pneumococcal diseases (IPDs), belonged to GPSC634-ST11189 and showed elevated minimum inhibitory concentrations for -lactams. Capsular switching events were observed between VTs and NVTs, highlighting the adaptability of pneumococcal populations. Antimicrobial non-susceptibility was highest for azithromycin (82.7%), followed by tetracycline (76.5%) and co-trimoxazole (70.4%), with higher rates observed in the post-PCV13 period. Notably, amoxicillin (=0.049) and meropenem (=0.002) showed significant non-susceptibility in the post-PCV13 period. Virulence factors and were associated with IPDs, while pilus islet PI-1-related genes were more frequent in non-invasive cases. These findings underscore the importance of genomic surveillance to monitor pneumococcal population dynamics and inform public health strategies. The inclusion of serotype 10A in the recently approved PCV20 offers promise for further reducing the global burden of IPDs, including in South Korea.

Funding
This study was supported by the:
  • Ministry of Health and Welfare (Award HI22C0117)
    • Principal Award Recipient: JungSeung-Hyun
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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/content/journal/mgen/10.1099/mgen.0.001433
2025-07-17
2026-04-22

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References

  1. Calvo-Silveria S, González-Díaz A, Grau I, Marimón JM, Cercenado E et al. Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study. Lancet Reg Health Eur 2024; 41:100913 [View Article] [PubMed]
    [Google Scholar]
  2. de Miguel S, Domenech M, González-Camacho F, Sempere J, Vicioso D et al. Nationwide trends of invasive pneumococcal disease in Spain from 2009 through 2019 in children and adults during the pneumococcal conjugate vaccine era. Clin Infect Dis 2021; 73:e3778–e3787 [View Article] [PubMed]
    [Google Scholar]
  3. Wahl B, O’Brien KL, Greenbaum A, Majumder A, Liu L et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15. Lancet Glob Health 2018; 6:e744–e757 [View Article] [PubMed]
    [Google Scholar]
  4. McLaughlin JM, Jiang Q, Isturiz RE, Sings HL, Swerdlow DL et al. Effectiveness of 13-valent pneumococcal conjugate vaccine against hospitalization for community-acquired pneumonia in older US adults: a test-negative design. Clin Infect Dis 2018; 67:1498–1506 [View Article] [PubMed]
    [Google Scholar]
  5. Sari RF, Fadilah F, Maladan Y, Sarassari R, Safari D. A narrative review of genomic characteristics, serotype, immunogenicity, and vaccine development of Streptococcus pneumoniae capsular polysaccharide. Clin Exp Vaccine Res 2024; 13:91–104 [View Article] [PubMed]
    [Google Scholar]
  6. Hyun H, Jang A-Y, Suh JW, Bae I-G, Choi WS et al. Community-acquired pneumococcal pneumonia in highly vaccinated population: analysis by serotypes, vaccination status, and underlying medical conditions. J Korean Med Sci 2023; 38:e330 [View Article] [PubMed]
    [Google Scholar]
  7. Lee MS. Invasive pneumococcal diseases in Korean adults after the introduction of pneumococcal vaccine into the national immunization program. Infect Chemother 2023; 55:411–421 [View Article] [PubMed]
    [Google Scholar]
  8. Choe YJ, Han MS, Choi YY, Sohn YJ, Kim YK et al. Trend change of nasopharyngeal colonization with Streptococcus pneumoniae and non-typeable Haemophilus influenzae in children attending daycare centres: nationwide population-based study, South Korea 2014 and 2019. Int J Infect Dis 2021; 111:328–332 [View Article] [PubMed]
    [Google Scholar]
  9. Kim CJ, Song J-S, Choi S-J, Song KH, Choe PG et al. Serotype distribution and antimicrobial susceptibilities of invasive Streptococcus pneumoniae isolates from adults in Korea from 1997 to 2012. J Korean Med Sci 2016; 31:715–723 [View Article] [PubMed]
    [Google Scholar]
  10. Geno KA, Gilbert GL, Song JY, Skovsted IC, Klugman KP et al. Pneumococcal capsules and their types: past, present, and future. Clin Microbiol Rev 2015; 28:871–899 [View Article] [PubMed]
    [Google Scholar]
  11. Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis 2010; 201:32–41 [View Article] [PubMed]
    [Google Scholar]
  12. Lo SW, Mellor K, Cohen R, Alonso AR, Belman S et al. Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study. Lancet Microbe 2022; 3:e735–e743 [View Article] [PubMed]
    [Google Scholar]
  13. Yang Baek J, Kim SH, Kang CI, Chung DR, Peck KR et al. Emergence of an extensively drug-resistant (XDR) Streptococcus pneumoniae serotype 15A by capsular switching. Int J Med Microbiol 2018; 308:986–989 [View Article] [PubMed]
    [Google Scholar]
  14. Baek JY, Kim SJ, Shin J, Chung Y-J, Kang C-I et al. Genome-wide analysis of the temporal genetic changes in Streptococcus pneumoniae Isolates of genotype ST320 and serotype 19A from South Korea. Microorganisms 2021; 9:9 [View Article] [PubMed]
    [Google Scholar]
  15. Yun KW, Rhie K, Kang JH, Kim K-H, Ahn JG et al. Emergence of serotype 10A-ST11189 among pediatric invasive pneumococcal diseases, South Korea, 2014-2019. Vaccine 2021; 39:5787–5793 [View Article] [PubMed]
    [Google Scholar]
  16. Kim GR, Kim E-Y, Kim SH, Lee HK, Lee J et al. Serotype distribution & antimicrobial resistance of Streptococcus pneumoniae causing invasive pneumococcal disease in Korea between 2017 and 2019 after introduction of the 13-valent pneumococcal conjugate vaccine. Ann Lab Med 2023; 43:45–54 [View Article] [PubMed]
    [Google Scholar]
  17. Humphries R, Bobenchik AM, Hindler JA, Schuetz AN. Overview of changes to the Clinical and Laboratory Standards Institute performance standards for antimicrobial susceptibility testing, M100, 31st edition. J Clin Microbiol 2021; 59:e0021321 [View Article] [PubMed]
    [Google Scholar]
  18. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article] [PubMed]
    [Google Scholar]
  19. Prjibelski A, Antipov D, Meleshko D, Lapidus A, Korobeynikov A. Using SPAdes de novo assembler. Curr Protoc Bioinformatics 2020; 70:e102 [View Article]
    [Google Scholar]
  20. Bosi E, Donati B, Galardini M, Brunetti S, Sagot M-F et al. MeDuSa: a multi-draft based scaffolder. Bioinformatics 2015; 31:2443–2451 [View Article] [PubMed]
    [Google Scholar]
  21. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  22. Hong E, Shin Y, Kim H, Cho WY, Song W-H et al. PneusPage: a web-based tool for the analysis of whole-genome sequencing data of Streptococcus pneumoniae. J Microbiol 2025; 63:e [View Article] [PubMed]
    [Google Scholar]
  23. Wood DE, Lu J, Langmead B. Improved metagenomic analysis with Kraken 2. Genome Biol 2019; 20:257 [View Article] [PubMed]
    [Google Scholar]
  24. Epping L, van Tonder AJ, Gladstone RA, Bentley SD, Page AJ et al. SeroBA: rapid high-throughput serotyping of Streptococcus pneumoniae from whole genome sequence data. Microb Genom 2018; 4: [View Article] [PubMed]
    [Google Scholar]
  25. Javaid N, Lo SW, Nisar MI, Basharat A, Jaleel H et al. Strain features of pneumococcal isolates in the pre- and post-PCV10 era in Pakistan. Microb Genom 2024; 10:10 [View Article] [PubMed]
    [Google Scholar]
  26. Jolley KA, Maiden MCJ. BIGSdb: scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics 2010; 11:595 [View Article] [PubMed]
    [Google Scholar]
  27. Gladstone RA, Lo SW, Lees JA, Croucher NJ, van Tonder AJ et al. International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact. EBioMedicine 2019; 43:338–346 [View Article] [PubMed]
    [Google Scholar]
  28. Lees JA, Harris SR, Tonkin-Hill G, Gladstone RA, Lo SW et al. Fast and flexible bacterial genomic epidemiology with PopPUNK. Genome Res 2019; 29:304–316 [View Article]
    [Google Scholar]
  29. Gladstone RA, Lo SW, Goater R, Yeats C, Taylor B et al. Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates. Microb Genom 2020; 6:6 [View Article] [PubMed]
    [Google Scholar]
  30. Liu B, Zheng D, Jin Q, Chen L, Yang J. VFDB 2019: a comparative pathogenomic platform with an interactive web interface. Nucleic Acids Res 2019; 47:D687–D692 [View Article] [PubMed]
    [Google Scholar]
  31. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article] [PubMed]
    [Google Scholar]
  32. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 2014; 30:1312–1313 [View Article] [PubMed]
    [Google Scholar]
  33. Argimón S, Abudahab K, Goater RJE, Fedosejev A, Bhai J et al. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microb Genom 2016; 2:e000093 [View Article] [PubMed]
    [Google Scholar]
  34. Cho EY, Choi EH, Kang JH, Kim K-H, Kim DS et al. Early changes in the serotype distribution of invasive pneumococcal isolates from children after the introduction of extended-valent pneumococcal conjugate vaccines in Korea, 2011-2013. J Korean Med Sci 2016; 31:1082–1088 [View Article] [PubMed]
    [Google Scholar]
  35. Mauffrey F, Fournier É, Demczuk W, Martin I, Mulvey M et al. Comparison of sequential multiplex PCR, sequetyping and whole genome sequencing for serotyping of Streptococcus pneumoniae. PLoS One 2017; 12:e0189163 [View Article] [PubMed]
    [Google Scholar]
  36. Maraki S, Mavromanolaki VE, Stafylaki D, Iliaki-Giannakoudaki E, Kasimati A et al. Antimicrobial resistance of Streptococcus pneumoniae clinical serotypes between 2017 and 2022 in Crete, Greece. Infect Chemother 2024; 56:73–82 [View Article] [PubMed]
    [Google Scholar]
  37. King AC, Kumar N, Mellor KC, Hawkins PA, McGee L et al. Comparison of gene-by-gene and genome-wide short nucleotide sequence-based approaches to define the global population structure of Streptococcus pneumoniae. Microb Genom 2024; 10:10 [View Article] [PubMed]
    [Google Scholar]
  38. Nagaraj G, Govindan V, Ganaie F, Venkatesha VT, Hawkins PA et al. Streptococcus pneumoniae genomic datasets from an Indian population describing pre-vaccine evolutionary epidemiology using a whole genome sequencing approach. Microb Genom 2021; 7:7 [View Article] [PubMed]
    [Google Scholar]
  39. Hanquet G, Krizova P, Dalby T, Ladhani SN, Nuorti JP et al. Serotype replacement after introduction of 10-valent and 13-valent pneumococcal conjugate vaccines in 10 countries, Europe. Emerg Infect Dis 2022; 28:137–138 [View Article] [PubMed]
    [Google Scholar]
  40. Eldholm V, Osnes MN, Bjørnstad ML, Straume D, Gladstone RA. A genome-based survey of invasive pneumococci in Norway over four decades reveals lineage-specific responses to vaccination. Genome Med 2024; 16:123 [View Article] [PubMed]
    [Google Scholar]
  41. Lo SW, Gladstone RA, van Tonder AJ, Lees JA, du Plessis M et al. Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study. Lancet Infect Dis 2019; 19:759–769 [View Article] [PubMed]
    [Google Scholar]
  42. von Mollendorf C, Mungun T, Ulziibayar M, Skoko P, Boelsen L et al. Effect of pneumococcal conjugate vaccine six years post-introduction on pneumococcal carriage in Ulaanbaatar, Mongolia. Nat Commun 2024; 15:6577 [View Article]
    [Google Scholar]
  43. Haranaka M, Young Song J, Huang K-C, de Solom R, Yamaji M et al. A phase 3 randomized trial of the safety and immunogenicity of 20-valent pneumococcal conjugate vaccine in adults ≥ 60 years of age in Japan, South Korea, and Taiwan. Vaccine 2024; 42:1071–1077 [View Article] [PubMed]
    [Google Scholar]
  44. Mellor KC, Lo S, Yoannes M, Michael A, Orami T et al. Distinct Streptococcus pneumoniae cause invasive disease in Papua New Guinea. Microb Genom 2022; 8:8 [View Article] [PubMed]
    [Google Scholar]
  45. Lo SW, Hawkins PA, Jibir B, Hassan-Hanga F, Gambo M et al. Molecular characterization of Streptococcus pneumoniae causing disease among children in Nigeria during the introduction of PCV10 (GSK). Microb Genom 2023; 9:9 [View Article] [PubMed]
    [Google Scholar]
  46. Rafiqullah IM, Varghese R, Hellmann KT, Velmurugan A, Neeravi A et al. Pneumococcal population genomics changes during the early time period of conjugate vaccine uptake in southern India. Microb Genom 2024; 10:10 [View Article] [PubMed]
    [Google Scholar]
  47. Lees JA, Croucher NJ, Goldblatt D, Nosten F, Parkhill J et al. Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration. elife 2017; 6:e26255 [View Article] [PubMed]
    [Google Scholar]
  48. Bentley SD, Lo SW. Global genomic pathogen surveillance to inform vaccine strategies: a decade-long expedition in pneumococcal genomics. Genome Med 2021; 13:84 [View Article] [PubMed]
    [Google Scholar]
  49. Park S-S, Gonzalez-Juarbe N, Martínez E, Hale JY, Lin Y-H et al. Streptococcus pneumoniae binds to host lactate dehydrogenase via PspA and PspC to enhance virulence. mBio 2021; 12:e00673-21 [View Article] [PubMed]
    [Google Scholar]
  50. Yamaguchi M, Hirose Y, Takemura M, Ono M, Sumitomo T et al. Streptococcus pneumoniae evades host cell phagocytosis and limits host mortality through its cell wall anchoring protein PfbA. Front Cell Infect Microbiol 2019; 9:301 [View Article] [PubMed]
    [Google Scholar]
  51. Song J-H, Chang H-H, Suh JY, Ko KS, Jung S-I et al. Macrolide resistance and genotypic characterization of Streptococcus pneumoniae in Asian countries: a study of the Asian Network for Surveillance of Resistant Pathogens (ANSORP). J Antimicrob Chemother 2004; 53:457–463 [View Article] [PubMed]
    [Google Scholar]
  52. Egorova E, Kumar N, Gladstone RA, Urban Y, Voropaeva E et al. Key features of pneumococcal isolates recovered in Central and Northwestern Russia in 2011-2018 determined through whole-genome sequencing. Microb Genom 2022; 8:8 [View Article] [PubMed]
    [Google Scholar]
  53. Almeida SCG, Lo SW, Hawkins PA, Gladstone RA, Cassiolato AP et al. Genomic surveillance of invasive Streptococcus pneumoniae isolates in the period pre-PCV10 and post-PCV10 introduction in Brazil. Microb Genom 2021; 7:7 [View Article] [PubMed]
    [Google Scholar]
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