Ferroptosis and iron-based therapies in Pseudomonas aeruginosa infections: From pathogenesis to treatment.

Abstract

Pseudomonas aeruginosa is a globally prevalent multidrug-resistant pathogen that causes severe infections, particularly in immunocompromised individuals. This review focuses on the dual role of iron in P. aeruginosa infections: as a critical nutrient for bacterial growth and as a mediator of host cell ferroptosis, a form of iron-dependent cell death. We summarize how P. aeruginosa manipulates iron metabolism to induce ferroptosis in host cells, thereby promoting its own survival and pathogenicity. Additionally, we explore therapeutic strategies targeting iron metabolism, including interfering with acquisition of iron ions from the environment, disrupting bacterial iron metabolism and iron homeostasis, using ferroptosis inhibitors to suppress host cell ferroptosis, and employing high iron concentrations to induce bacterial ferroptosis. These insights provide innovative approaches to combat drug-resistant P. aeruginosa infections.