Yersiniabactin produced by Escherichia coli promotes intestinal inflammation by inducing lipid peroxidation and ferroptosis

Escherichia coli (E. coli), a major foodborne pathogen, is a significant threat to public health, causing food poisoning and animal diseases. Therefore, it is imperative to further investigate the impacts of E. coli on gut health. Yersiniabactin (Ybt), a siderophore produced by E. coli, depletes iron from host cells, leading to cellular damage and death. However, the precise mechanisms underlying its pathogenicity remain unclear. This study explores how E. coli-Ybt contributes to intestinal inflammation by inducing ferroptosis.Our findings show that E. coli-Ybt intensifies oxidative stress, lipid peroxidation, inflammation, iron accumulation, and cell death, culminating in intestinal injury. Mechanistically, Ybt-mediated ferroptosis is linked to the suppression of the Keap1/Nrf2 pathway, which amplifies reactive oxygen species (ROS), and the activation of the TNF/NF-κB pathway, driving inflammation. ROS-induced oxidation of polyunsaturated fatty acids (PUFAs) promotes lipid peroxidation and the production of 6-trans-leukotriene B4 (6-transLTB4) via the arachidonic acid pathway, further triggering ferroptosis. Exogenous 6-transLTB4 exacerbates this inflammatory cascade. Additionally, Ybt disrupts iron efflux, leading to excessive intracellular iron accumulation.Ybt significantly aggravates intestinal inflammation by inducing ferroptosis in intestinal epithelial cells, enhancing the pathogenicity of E. coli. This underscores the potential threat of E. coli to intestinal health, emphasizing the significance of Ybt-induced ferroptosis.