UspF Regulates Type III Pili-Mediated Adhesion, Oxidative Stress Resistance, and Virulence in Klebsiella pneumoniae

TL;DR

This study shows that the UspF protein in Klebsiella pneumoniae is crucial for adhesion, stress resistance, and virulence, making it a potential target for new treatments.

Contribution

The study identifies UspF as a novel regulator of adhesion, oxidative stress resistance, and virulence in Klebsiella pneumoniae.

Findings

UspF deletion reduces adhesion to human airway epithelial cells and downregulates type III pili genes.

UspF deficiency increases susceptibility to oxidative stress and immune cell phagocytosis.

UspF deletion significantly attenuates virulence in a mouse model of K. pneumoniae infection.

Abstract

Klebsiella pneumoniae (K. pneumoniae, KP) is a significant opportunistic pathogen responsible for both nosocomial and community-acquired infections. Bacterial adhesion is the critical initial step for host colonization and the establishment of disease. In this study, we utilized a mariner transposon mutagenesis system to construct a mutant library from the clinical KP strain KP20, identifying a mutant with significantly impaired epithelial cell adhesion due to an insertion in the uspF gene. Genetic knockout experiments confirmed that uspF deletion markedly reduced the adhesion to human airway epithelial cells (Calu-3) and downregulated the transcription of type III pili-encoding genes (mrkABDF). Furthermore, uspF deficiency compromised antioxidant stress and serum resistance and increased susceptibility to dendritic cell and macrophage phagocytosis. In vivo challenge experiments further demonstrated that uspF deletion significantly attenuated K. pneumoniae virulence in mice. These findings provide important insights into the molecular pathogenesis of K. pneumoniae and identify UspF as a potential target for therapeutic intervention.

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