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Genomic Characterization of Klebsiella pneumoniae Causing Invasive Disease in South African Infants: Observational
Courtney P Olwagen1, Alane Izu1, Shama Khan1
1South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa.
Insights
Genomic sequencing of invasive Klebsiella pneumoniae in African infants revealed dominant strains and high multidrug resistance, including carbapenem resistance. Findings highlight key targets for potential vaccine development against this critical pathogen.
Area of Science:
- Microbiology
- Genomics
- Epidemiology
Background:
- Klebsiella pneumoniae (KPn) is a major cause of invasive bacterial disease in African children.
- There is limited genotypic characterization of KPn strains causing invasive disease in this population.
Purpose of the Study:
- To perform genotypic characterization of invasive Klebsiella pneumoniae isolates from infants in Africa.
- To identify dominant strains, antimicrobial resistance patterns, and potential vaccine targets.
Main Methods:
- Whole-genome sequencing of 337 invasive KPn isolates from infants (≤90 days) collected via hospital surveillance and postmortem sampling.
- Genomic analysis to determine clonotypes, sequence types (STs), K-loci (KLs), and O-antigens.
- Detection of antimicrobial resistance genes, including those conferring carbapenem resistance.
Main Results:
- Sequence type 17 (22.0%) and ST39 (12.7%) were the predominant clonotypes.
- Dominant K-loci included KL25 (24.0%), KL2 (14.5%), and KL149 (13.4%), with O1αβ,2α and O5 as major O-antigens.
- Eighty-five percent of isolates harbored multidrug resistance genes; 32.9% showed carbapenem resistance, with blaOXA-181 being the most common carbapenemase gene.
Conclusions:
- Invasive KPn disease in African infants is associated with diverse strains, but over 80% are linked to 11 K-loci.
- These findings offer crucial insights into KPn epidemiology in African children.
- The identified K-loci represent potential targets for vaccine development to combat invasive KPn infections.
Background:
Klebsiella pneumoniae (KPn) is a leading cause of invasive bacterial disease in African children, albeit with a scarcity of genotypic characterization.
Methods:
We sequenced invasive KPn isolates from infants ≤90 days, collected through observational hospital surveillance (n = 226) between March 4, 2019 and February 27, 2021, and between May 13, 2022 and October 31, 2023, and postmortem sampling (n = 111) between February 15, 2018 and April 18, 2023. Postmortem Kpn isolates were attributed in the causal pathway to death by the determination of the cause of death panel, which consists of local experts.
Results:
Three hundred and thirty-seven isolates (226 identified during hospital surveillance and 111 from postmortem sampling) were included in the final analysis. Genomic analysis identified 85 distinct clonotypes. Sequence type (ST) 17 (22.0%) predominated, followed by ST39 (12.7%). The dominant K-locus (KL) were KL25 (24.0%), KL2 (14.5%), and KL149 (13/4%), while the dominant O-antigens included O1αβ,2α(48.4%), and O5 (19.9%). Eighty-five percent (287/337) of the KPn isolates harbored multidrug resistant genes, including 32.9% to carbapenems. Notably, blaOXA-181, blaNDM-5, and blaNDM-1 were detected in 26.4%, 2.1% (7/337), and 0.3% (1/337) of isolates, respectively.
Conclusions:
Although a wide diversity of strains were associated with Kpn invasive disease, over 80% of the cases were attributed to 11 K loci. These data provide critical insights into KPn epidemiology and highlight potential antigen targets for vaccine development in young African children.
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