Molecular Profiling of a Multi-Strain Hypervirulent Klebsiella pneumoniae Infection Within a Single Patient

Abstract

Background:The rising prevalence of infections caused by carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) has outpaced our understanding of their evolutionary diversity. By straining the antimicrobial options and constant horizontal gene transfer of various pathogenic elements, CR-hvKP poses a global health threat. Methods: Six KP isolates (KP1~KP6) from urine, sputum and groin infection secretion of a single patient were characterized phenotypically and genotypically. The antimicrobial susceptibility, carbapenemase production, hypermucoviscosity, serum resistance, virulence factors, MLST and serotypes were profiled. Genomic variations were identified by whole-genome sequencing and the phylogenetic differentiation was analyzed by Enterobacterial repetitive intergenic consensus (ERIC)-PCR. Results: All KP strains were multi-drug resistant. Four of them (KP1, KP3, KP5 and KP6) belonged to ST11-K64, with high genetic closeness (relatedness coefficient above 0.96), sharing most resistance and virulence genes. Compared with KP1, the later isolates KP3, KP5 and KP6 acquired bla KPC-1 and lost bla SHV-182 genes. KP2 and KP4 had the same clonal origin of ST35-K16 (relatedness coefficient 0.98), containing almost identical genes for resistance and virulence. They were non-mucoid and carried bla NDM-5 gene. Conclusion:A co-infection with two types of CR-hvKP affiliated with different clades within a single patient amplified the treatment difficulties. In addition to source control and epidemiological surveillance, investigation of the in-host interactions between CR-hvKP variants may provide valuable treatment solutions.