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Molecular Profiling of a Multi-Strain Hypervirulent Klebsiella pneumoniae Infection Within a Single Patient
Huijun Cao1, Shiwei Liang1,2, Chenchen Zhang2
1Centre for Clinical Laboratories, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, People's Republic of China.
Background:
The rising prevalence of infections caused by carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) has outpaced our understanding of their evolutionary diversity. By straining the antimicrobial options and constant horizontal gene transfer of various pathogenic elements, CR-hvKP poses a global health threat.
Methods:
Six KP isolates (KP1~KP6) from urine, sputum and groin infection secretion of a single patient were characterized phenotypically and genotypically. The antimicrobial susceptibility, carbapenemase production, hypermucoviscosity, serum resistance, virulence factors, MLST and serotypes were profiled. Genomic variations were identified by whole-genome sequencing and the phylogenetic differentiation was analyzed by Enterobacterial repetitive intergenic consensus (ERIC)-PCR.
Results:
All KP strains were multi-drug resistant. Four of them (KP1, KP3, KP5 and KP6) belonged to ST11-K64, with high genetic closeness (relatedness coefficient above 0.96), sharing most resistance and virulence genes. Compared with KP1, the later isolates KP3, KP5 and KP6 acquired bla KPC-1 and lost bla SHV-182 genes. KP2 and KP4 had the same clonal origin of ST35-K16 (relatedness coefficient 0.98), containing almost identical genes for resistance and virulence. They were non-mucoid and carried bla NDM-5 gene.
Conclusion:
A co-infection with two types of CR-hvKP affiliated with different clades within a single patient amplified the treatment difficulties. In addition to source control and epidemiological surveillance, investigation of the in-host interactions between CR-hvKP variants may provide valuable treatment solutions.
Insights
Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) strains evolved within a single patient, complicating treatment. Understanding their in-host evolution is key to developing new therapeutic strategies against these dangerous pathogens.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Rising prevalence of carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) strains presents a significant global health threat.
- CR-hvKP infections are challenging due to antimicrobial resistance and rapid horizontal gene transfer.
- Understanding the evolutionary diversity of CR-hvKP is crucial for effective treatment and control.
Purpose of the Study:
- To investigate the genotypic and phenotypic characteristics of CR-hvKP isolates from a single patient.
- To analyze the evolutionary dynamics and genetic relatedness of CR-hvKP strains within a host.
- To identify resistance and virulence gene acquisition/loss during CR-hvKP evolution.
Main Methods:
- Phenotypic and genotypic characterization of six Klebsiella pneumoniae isolates.
- Antimicrobial susceptibility testing, carbapenemase production, hypermucoviscosity, and virulence factor profiling.
- Whole-genome sequencing and Enterobacterial repetitive intergenic consensus (ERIC)-PCR for genomic variation and phylogenetic analysis.
Main Results:
- All isolates were multi-drug resistant. Four strains (KP1, KP3, KP5, KP6) belonged to ST11-K64, showing high genetic relatedness and sharing resistance/virulence genes.
- Later isolates (KP3, KP5, KP6) acquired blaKPC-1 and lost blaSHV-182 compared to KP1.
- Two strains (KP2, KP4) belonged to ST35-K16, were non-mucoid, carried blaNDM-5, and exhibited high genetic similarity.
Conclusions:
- Co-infection with distinct CR-hvKP clades within a single patient significantly complicates treatment.
- Epidemiological surveillance and source control are essential for managing CR-hvKP outbreaks.
- Investigating in-host interactions among CR-hvKP variants may reveal novel therapeutic targets.
