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Emergence of a Superplasmid Coharboring Hypervirulence and Multidrug Resistance Genes in Klebsiella pneumoniae Poses New Challenges to Public Health

Jia X, Zhu Y, Jia P, Liu X, Yu W, Li X, Xu Y, Yang Q

Microbiology spectrum, 2022

Abstract

The emergence of plasmids coharboring hypervirulence (Hv) and multidrug resistance (MDR) genes has further accelerated the spread of MDR-Hv Klebsiella pneumoniae (MDR-HvKP) strains, having a severe impact on public health. Here, we report an MDR-Hv superplasmid coharboring hypervirulence and MDR genes and the detailed characterization of its genetic and phenotypic features. This plasmid was identified in an ST11 (sequence type 11)-K64 carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) strain, SZS128, which was responsible for a bloodstream infection in a 21-year-old female. Susceptibility testing showed that SZS128 was resistant to amikacin, levofloxacin, and almost all of the β-lactams examined. SZS128 showed high virulence in a Galleria mellonella survival assay and a mouse intraperitoneal infection model. Genomic analysis showed that SZS128 not only possessed a KPC plasmid (pSZS128-KPC) but also carried a superplasmid (pSZS128-Hv-MDR) coharboring hypervirulence and MDR genes and possessing complete conjugative regions. Conjugation and transformation assays confirmed the potential for horizontal transfer and the high stability (retention rate of >95%) of the pSZS128-Hv-MDR superplasmid. Furthermore, growth curve assessment confirmed that there was no increase in the fitness cost in the presence of pSZS128-Hv-MDR. Therefore, we define a superplasmid as a plasmid fulfilling all the following criteria: (i) a single plasmid that coharbors hypervirulence and MDR genes,…

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