Phenotypic and Genomic Characterization of Virulence Heterogeneity in Multidrug-Resistant ST11 Klebsiella pneumoniae During Inter-Host Transmission and Evolution.

Abstract

BackgroundMultidrug-resistant (MDR) ST11 hypervirulent Klebsiella pneumoniae (hvKp) is emerging in China.PurposeThe aim of this study was to track the transmission and evolution of hvKp.Materials and MethodsA retrospective study focused on Kp infection was conducted. Clinical data were collected from electronic medical records. Whole-genome sequencing of Kp strains was performed. Single-nucleotide polymorphisms (SNPs) were analyzed and a transmission map was constructed. Sequence type, and antimicrobial and virulence-associated genes were characterized. Strains with some combination of the virulence genes, prmpA, prmpA2, iucA, iroB, and peg-344, were defined as hvKp. Kp virulence phenotypes were evaluated using the Galleria mellonella model.ResultsAll 33 Kp strains were MDR-Kp and 13 (39.4%) were hvKp. Most hvKp strains (84.6%, 11/13) were hospital-acquired infections (HAIs). Two unique combinations of virulence-associated genes were detected among hvKp strains. Eleven cases were associated with prmpA2+iucA and two strains presented with peg-344+prmpA+prmpA2+iucA. Surprisingly, two community-acquired MDR-hvKp infection cases were identified. Eight hvKp strains (61.5%, 8/13) exhibited a hypervirulent phenotype in the G. mellonella model. Five MDR-hvKp strains with the hypervirulence phenotype originated from a single cluster. Additionally, nine clones were identified among the two clades, six of which were hvKp. Moreover, the hvKp in clade 1 carried the IncHI1B plasmid replicon, whereas none of the hvKp strains in clade 2 harbored IncHI1B. These data, showing that different hvKp clones distributed into separate clades, indicate that transmission and evolution occurred within the hospital.ConclusionDuring inter-host evolution and transmission, various virulence clusters of the epidemic clone, MDR-ST11, converged, conferring phenotypic virulence heterogeneity and spread within the hospital and possibly the community. Mobile/conjugative genetic elements associated with virulence-encoding gene clusters might emerge and have been transmitted within the hospital, suggesting that enhanced ongoing surveillance is essential.