Review decodes *Klebsiella pneumoniae* manipulation of pyroptosis, apoptosis, and necroptosis for sepsis therapy.

Klebsiella pneumoniae (Kp) is a critical Gram-negative opportunistic pathogen, posing a severe global public health threat, particularly in healthcare settings. It is a leading cause of hospital-acquired infections, including pneumonia, urinary tract infections, and bacteremia, with mortality rates reaching 50–100% in individuals with underlying conditions and septicemia. The alarming rise of multidrug-resistant (MDR) and carbapenem-resistant Kp (CR Kp) underscores an urgent need for novel therapeutic strategies, as antibiotic susceptibility has drastically declined (e.g., piperacillin–tazobactam from 42.6% to 26.5%). A key aspect of Kp pathogenesis is its ability to manipulate host cell death pathways, which facilitates immune evasion and disease progression.

This comprehensive review synthesizes current understanding of host–pathogen dynamics in Klebsiella pneumoniae infections, specifically focusing on the mechanisms by which Kp regulates host cell death. The authors analyzed existing literature detailing Kp's manipulation of pyroptosis, apoptosis, and necroptosis pathways. The scope included studies elucidating inflammasome activation, caspase-1 cleavage, and the release of pro-inflammatory cytokines, as well as investigations into emerging host-directed therapeutic approaches for sepsis that target these cellular processes.