Phenotype and Antibiotic Resistance Switching in Hypervirulent Klebsiella pneumoniae

Phenotypic variation, including reduced capsule production, is common in Enterobacteriaceae.In this study, we investigated phenotypic switching in hypervirulent Klebsiella pneumoniae (hvKp).We observed irregular colony morphology, with small colonies displaying reduced mucoviscosity, and identified three variantsparental (mucoid), mixed (nonmucoid, heterogeneous), and a stable small-colony variant (SCV, nonmucoid).Gene expression analysis revealed no significant differences in the expression of capsule and virulence genes between the altered colonies and the parental strain.Multiplex polymerase chain reaction (PCR) confirmed identical virulence-gene profiles across 11 targets.Antimicrobial susceptibility testing demonstrated a graded increase in polymyxin B resistance in phenotypically altered colonies (parental < mixed < SCV), whereas colistin susceptibility differed among variants, with the mixed population exhibiting increased susceptibility.All variants were susceptible to gentamicin and meropenem.Furthermore, functional assays using murine macrophages showed that nonmucoid variants exhibited significantly enhanced phagocytosis and intracellular survival compared with the mucoid parental strain.These findings highlight the dynamic phenotypic plasticity of hvKp and suggest that capsule-deficient variants acquire distinct survival advantages within host cells, accompanied by altered antimicrobial resistance profiles and trade-offs between extracellular immune evasion and intracellular persistence.