Advances in Pseudomonas aeruginosa-Induced Programmed Cell Death and Potential Targeted Treatment Strategies.

Pseudomonas aeruginosa (P. aeruginosa) is responsible for the high prevalence of various nosocomial infections, and it is challenging to completely eradicate P. aeruginosa infection in clinics. One of P. aeruginosa's main pathogenic mechanisms is to trigger multiple forms of programmed cell death (PCD), such as apoptosis, pyroptosis, necroptosis, ferroptosis, and PANoptosis, among which PANoptosis is a newly discovered PCD pathway mediated by PANoptosome complexes and their key upstream regulators. Compared with other well-studied PCD pathways, advances in P. aeruginosa-induced PANoptosis have yet to be thoroughly reviewed. This review highlights research advances in this pathway, providing mechanistic insights by summarizing the upregulation and/or activation of PANoptosome sensor proteins and their key upstream regulators during P. aeruginosa infection. We also offer perspectives on the mechanistic links between P. aeruginosa cytotoxicity and other forms of PCD. Additionally, pharmacological compounds that may be used to target P. aeruginosa-induced PCD, particularly PANoptosis, are discussed, and future research and therapeutic directions are proposed. Our work helps bridge the knowledge gap, paving the way for further understanding of P. aeruginosa-induced PCD and the development of novel therapeutics against P. aeruginosa infection.