Klebsiella pneumoniae: Host interactions, virulence mechanisms, and novel therapeutic strategies

Abstract

K. pneumoniae has emerged as a major infectious threat due to its remarkable capacity for intracellular survival, virulence, and antibiotic resistance. It evades immune clearance by resisting phagocytosis through capsular polysaccharides and lipopolysaccharides, modulating macrophage polarization to create a permissive intracellular niche, and autophagic degradation. Additionally, it alters cytokine responses and interferes with host cell death pathways like apoptosis and pyroptosis to suppress inflammasome activation and efferocytosis. These immune evasion strategies are particularly concerning in the context of emerging MDR and hypervirulent strains. In response, host directed therapies (HDTs), including epigenetic and immunomodulatory interventions, offer promising non-antibiotic based strategies. Understanding the host pathogen interaction is essential to guide future therapeutic development.

Keywords: Apoptosis; Autophagy; Host directed therapy; Immunomodulation; Inflammasome; K. pneumoniae, intracellular survival; Macrophage polarization; Pyroptosis.