The rise of multidrug-resistant bacteria presents a critical global health threat, demanding innovative therapeutic approaches. This review highlights the key findings on ferroptosis - a novel iron-dependent cell death pathway - as a promising strategy for combating bacterial infections and resistance. Central to ferroptosis are iron-mediated lipid peroxidation and reactive oxygen species (ROS) accumulation, which exert antimicrobial effects through 2 primary mechanisms: host cell ferroptosis triggering lipid peroxidation and direct ferroptosis-like bacterial death induced by ferrous iron. Lizeng Gao demonstrate that nanotechnology can enhance ferroptosis-based therapy by enabling targeted drug delivery, minimizing off-target effects, and improving efficacy against resistant bacteria. Additionally, polysulfides amplify ferroptotic activity by suppressing bacterial antioxidant defenses, reducing the need for high doses of ferroptosis inducers. Compared to conventional antibiotics, ferroptosis offers distinct advantages in overcoming resistance mechanisms. However, challenges remain, including the complexity of iron metabolism and potential toxicity, which must be addressed for clinical translation. Future research should focus on elucidating ferroptosis mechanisms and advancing delivery technologies, such as nanoparticle-based systems, to optimize precision and efficacy in vivo. These insights position ferroptosis as a viable alternative for treating resistant infections, pending further refinement.
Keywords: antibacterial therapy; ferroptosis; multidrug resistance; nanotechnology.
Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.