The Emergence of Highly Resistant and Hypervirulent Klebsiella pneumoniae CC14 Clone in a Tertiary Hospital over Eight Years
Background: Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks.
Methods: In this study, we conducted an in-depth genomic analysis on a large-scale collection of 332 multidrug-resistant K. pneumoniae strains recovered from 243 patients from a single major hospital in the west of Saudi Arabia from 2014 through 2022. We employed a broad range of phylogenetic and phylodynamic methods to understand the evolution of the significant clones on epidemiological time scales, virulence and resistance determinants, and their dynamics. We also integrated the genomic data with detailed electronic health record (EHR) data for the patients to understand the clinical implications of the resistance and virulence of different strains.
Findings: We discovered a diverse population underlying the infections, with most strains belonging to Clonal Complex 14 (CC14) exhibiting dominance. Specifically, we observed the emergence and continuous expansion of strains belonging to the dominant ST2096 in the CC14 clade across hospital wards in recent years. These strains acquired resistance mutations against Colistin and ESBL and carbapenemase genes, namely blaOXA-48 and blaOXA-232, located on three distinct plasmids, on epidemiological time scales. Strains of ST2096 exhibited a higher virulence level with the presence of the siderophore Aerobactin (iuc) gene situated on the same mosaic plasmid as ESBL resistance gene. Integration of ST2096 with EHR data confirmed the significant link between colonization by ST2096 and the diagnosis of sepsis and elevated in-hospital mortality.
Interpretation: Overall, these results demonstrate the clinical significance of ST2096 clones and illustrate the rapid evolution of an emerging hypervirulent and MDR K. pneumoniae in a clinical setting.
| File Name | Description |
|---|---|
| Kaptive_results.csv | Capsule typing results from Kaptive |
| Klaborate_results.txt | Klaborate report |
| NDM_plasmid.gbk | Gene Bank File for the Hl1B plasmid |
| OXA232_plasmid.gbk | Gene Bank File for the Bla-OXA232 plasmid |
| OXA48_plasmid.gbk | Gene Bank File for the Bla-OXA48 plasmid |
| assembly_stats.txt | Assembly statistics |
| gene_presence_absence_roary_plasmid.csv | Pangenome file for the H1lB plasmids |
| mlst_output.csv | MLST results |
For inquiries regarding this research, please contact:
Danesh Moradigaravand
Email: danesh.moradigaravand@kaust.edu.sa
Assistant Professor and Group Leader
Infectious Disease Epidemiology
Biological and Environmental Science and Engineering (BESE) Division
Lab website: https://ide.kaust.edu.sa/
King Abdullah University of Science and Technology (KAUST)
Thuwal
Saudi Arabia