Abstract
Background
Hypervirulent Klebsiella pneumoniae (hvKP) has been described as an invasive syndrome of liver abscess and metastatic infection in Asia, and this syndrome is emerging globally.
Methods
This study examined the association between disease phenotypes and genotypic markers of hypervirulence in 273 isolates of Klebsiella pneumoniae (KP) collected from invasive infections across three hospitals in Hong Kong between 2019 and 2023. Whole genome sequencing was analysed by Kleborate and Kaptive. Epidemiological background, disease phenotype, virulence genes, and antimicrobial susceptibility were analysed. Genotypically defined hvKP (g-hvKP) were defined as having iucA, iroB, rmpA, rmpA2, and peg-344. Others were defined as classical Klebsiella pneumoniae (cKP). Genome-wide association study (GWAS) was performed to identify additional genes associated with hvKP.
Results
The commonest K types are K2 (13.9%) and K1 (10.6%). The commonest ST is ST 23 (8.8%). g-hvKP represents 20.8% of all isolates. The ESBL phenotype is more likely in cKP than g-hvKP (22% vs 9%, p = 0.04). g-hvKP are more susceptible to cephalosporins (p = 0.02) and fluoroquinolones (p = 0.01). Among liver abscess cases, 49% of them are c-KP. g-hvKP is associated with neither mortality, disease severity, nor metastatic infection. g-hvKP has a sensitivity of 46% and a specificity of 86% in detecting liver abscesses or metastatic infections. By omitting rmpA2, F1 score improves from 0.46 to 0.51. GWAS reveals cysH3, pfeA2, and aidA as additional candidate genes linked to hvKP.
Conclusion
Significant overlap in disease phenotype exists between cKP and g-hvKP. Additional candidate genes linked to hvKP are cysH3, pfeA2, and aidA.
Plain language summary
The bacterial pathogen Klebsiella pneumoniae (Kp) can cause dangerous, invasive infections in hospitals. A subset of infections with a “hypervirulent” form of Kp are particularly dangerous, but exact definitions of what constitutes hypervirulent Kp are still in question. In this study of 273 serious Kp infections, we found that only 1 in 5 cases carried the classic hypervirulent DNA markers. We also found that among the most severe liver damage seen in infection, only half of cases were caused classically defined hypervirulent Kp. The classical DNA-based definition also was not able to predict disease severity. We found non-classical DNA markers among these serious infections, suggesting the old definition of “hypervirulent” Kp needs updating.
Similar content being viewed by others
Acknowledgements
The authors would like to acknowledge the support of laboratory staff in the Department of Microbiology of the Prince of Wales Hospital. The authors would also like to acknowledge the help from Mr Zhi Cheng Ye for his assistance in the study. We acknowledge the funding bodies for supporting this project. This work was supported by the RGC Theme-based Research Scheme Project [grant number: T11-104/22-R] (co-PI, M.I.) and the Food and Health Bureau, Government of Hong Kong Special Administration Region and Health and Medical Research Fund (H.M.R.F.) [grant number: CID-CUHK-C] (PI:M.I.). The funding bodies were not involved in the study’s design, data collection, analysis or interpretation of data or in manuscript writing.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Lee, A.LH., Li, C., Ng, R.W. et al. Revisiting definitions of hypervirulent and classical Klebsiella pneumoniae through virulence factors and disease phenotype. Commun Med (2026). https://doi.org/10.1038/s43856-026-01613-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s43856-026-01613-7
