Genomic diversity and phenotypic heterogeneity of Klebsiella pneumoniae isolates causing bloodstream infection in an infectious disease hospital in Ho Chi Minh City, Vietnam

Klebsiella pneumoniae has been traditionally considered an opportunistic pathogen, now otherwise healthy individuals commonly present with K. pneumoniae blood infections, which can result in serious complications such as liver abscesses and septic shock. Consequently, the bacterium has become a leading cause of human disease. Along with classical K. pneumoniae (cKp), which is an important reservoir of antimicrobial resistance (AMR) genes, hypervirulent K. pneumoniae (hvKp) is increasingly becoming of high clinical concern because it carries numerous virulence factors. A high proportion of bloodstream infections (BSIs) in Vietnam are associated with K. pneumoniae, with the epidemiology, population structures and transmission dynamics of hvKp being well described. However, little is known about how virulence-associated traits contribute to increased pathogenicity in this setting and which genetic determinants may be attributable to the virulence variation. In this cross-sectional study, we used a subset of clinical isolates to define the genomic structure and population of K. pneumoniae BSI isolates and additionally comprehensively characterised specific phenotypic features of hvKp associated with clinical manifestations. A genomic analysis of 83 random selected K. pneumoniae BSI isolates defined that lineage of KpI was the most common lineage (91.5%). The hypervirulent sequence type 23 (ST23) was the most prevalent (18.5%), followed by the multidrug resistance (MDR) lineages ST15 and ST17 (7.7% each). Specific hvKp ST23 phenotypic virulence assays showed considerable variation in virulence potential despite possessing a comparable compendium of virulence factors. Comprehensive analysis of genomic variations across the ST23 isolates revealed different genetic backgrounds and distinct mutations occurred on essential genes that might be involved the obsereved phenotypic diversity. These findings show the pathogenic potential of hvKp isolates from Vietnam, and also highlight the need for improved phenotype prediction to understand the clinical threat from strains in this groups.