The capsule of hypervirulent Klebsiella pneumoniae maintains neutrophils in neutral activation state

Abstract

Hypervirulent Klebsiella pneumoniae (hvKp) cause invasive infections despite robust neutrophil recruitment, yet the mechanisms enabling persistence in neutrophil-rich environments remain poorly defined. Here, we show that hvKp do not simply resist neutrophil antimicrobial mechanisms but instead constrain neutrophils into a neutral functional state characterised by limited bactericidal activity. Using genetic dissection of the rmpADC locus, pharmacological inhibition of neutrophil effector pathways, and analysis of a diverse panel of clinical isolates, we demonstrate that rmpADC-driven capsule properties uncouple neutrophil recognition and activation from bacterial killing. Deletion of rmpADC restores phagocytosis, degranulation, and intraphagosomal killing, whereas loss of individual rmpD or rmpC permits neutrophil activation without bacterial killing. Moreover, hypermucoviscosity alone is sufficient to protect bacteria from neutrophil-mediated killing across multiple genetic backgrounds. Together, these findings identify capsule-driven immune state control as a central mechanism of hvKp neutrophil evasion and reveal distinct thresholds governing neutrophil activation and bactericidal outcome.