Deciphering the genomic landscape of hypervirulent Klebsiella pneumoniae in South African tertiary hospitals

Hypervirulent Klebsiella pneumoniae (hvKp) is an emerging pathogen causing severe infections globally, yet genomic data from inland South African regions remain limited, hindering understanding of local hvKp diversity and virulence. Elevenhypermucoviscous Klebsiella pneumoniae isolates collected in 2021 and 2024 were subjected to WGS. Genomes were assembled and analysed for sequence types, capsular loci, virulence, and antimicrobial resistance genes using established bioinformatics pipelines, with phylogenomic relationships inferred by core genome analysis against representative global reference strains. Whole genome sequence (WGS) analyses confirmed the presence of several signature genes for the eleven hypermucoviscous isolates studied in this cohort, isolated in 2021 and in 2024. Among them, the most prevalent virulence determinants were the siderophores included loci ybt (10/11, 90%), irp2 (4/11, 37%), and the capsule regulator genes rmpA (3/11, 27%) and rmpA2 (1/11,9%) The most dominant serotype (ST) among the hypermucoviscous Klebsiella pneumoniae isolates was ST3430 (3/11, 27%), capsule type K17. ST23 capsule type K1 was observed in one isolate (1/11, 9%). Of equal importance, other isolates belonging to international high-risk sequence types, ST14 and ST86-K2, were identified in one isolate each of the respective STs. Antimicrobial resistance genes were limited, mainly involving efflux pumps and metal resistance systems. Importantly, no carbapenem and extended-spectrum beta-lactam resistance was detected. Phylogenomic analysis revealed substantial genetic diversity and close relationships across multiple internationally disseminated lineages originating from East Asia, South Asia, North Africa, and Europe, highlighting substantial global lineage diversity within the cohort. These findings enhance understanding of hvKp genomic diversity in South Africa and highlight the need for ongoing genomic surveillance to detect potential convergence of virulence and resistance traits that may threaten clinical management and emphasize the need for genomic epidemiology as part of the diagnostic routine.