Genomic landscape of hypervirulent Klebsiella pneumoniae (hvKp) in Bangladesh: comparative analysis with global hvKp lineages

Abstract

Hypervirulent Klebsiella pneumonia (hvKp) has emerged as a major global public health concern due to its ability to cause severe, invasive infections and its increasing convergence with antimicrobial resistance (AMR). While hvKp has been extensively studied in East and Southeast Asia, genomic data from South Asia, particularly Bangladesh remain limited. This thesis presents a comprehensive comparative genomic analysis of hvKp isolates from Bangladesh in a global context, focusing on population structure, virulence determinants, antimicrobial resistance profiles, and capsular diversity. Using publicly available whole-genome sequencing data from the Pathogen Watch platform, a total of 20,430 K. pneumoniae genomes were analyzed, including 601 isolates from Bangladesh. Hypervirulent strains were defined using established genomic markers, primarily the presence of the aerobactin (iuc) locus, ensuring high specificity. Comparative analyses were conducted between Bangladeshi and global isolates using sequence typing, virulence scoring, resistance burden metrics, and multivariate statistical approaches. The results reveal that the K. pneumoniae population in Bangladesh represents a limited subset of global diversity, dominated by a small number of enriched sequence types, notably ST11, ST16, ST48, and ST147. Hypervirulent strains accounted for only 4.5% of Bangladeshi isolates, substantially lower than the global average. Bangladeshi hvKp exhibited strong enrichment of key virulence loci, including aerobactin, yersiniabactin, and rmpA/rmpA2, but showed lower prevalence of colibactin compared to global hvKp populations. Although Bangladeshi hvKp isolates demonstrated high levels of multidrug resistance—particularly to aminoglycosides, fluoroquinolones, and sulfonamides—the prevalence of carbapenem-resistant hvKp remained low. Capsular and O-antigen analyses identified a distinctive regional serotype profile dominated by K20, K2, and O1 variants, differing markedly from global patterns. Multivariate analyses confirmed that Bangladeshi hvKp form a genetically constrained 5 cluster with limited virulence–AMR convergence. Overall, this study highlights Bangladesh as being in an early epidemiological phase of hvKp evolution, presenting a critical opportunity for targeted surveillance, antimicrobial stewardship, and region-specific intervention strategies before the widespread emergence of highly resistant hypervirulent clones