Ferroptosis-Like Death: An Emerging Innovative Antibacterial Strategy

The increasing global crisis of antibiotic resistance underscores the imperative for innovative antibacterial strategies that transcend conventional mechanisms. Ferroptosis, an iron-dependent form of regulated cell death characterized by lethal lipid peroxidation, is a promising therapeutic approach. This review systematically explores ferroptosis-like death as an emerging antibacterial paradigm. The core mechanism involves exogenous interventions that result in intracellular iron overload, the incorporation of polyunsaturated fatty acids (PUFAs), and the disruption of bacterial antioxidant defenses. A comprehensive evaluation of three key strategies is provided: host-directed approach, in which immune cells are programmed to eliminate intracellular pathogens; small molecule-induced pathway, in which iron agents, PUFAs, and others are used to directly trigger bacterial death; and nanomaterial-mediated precision therapy, in which functionalized nanosystems are employed for synergistic and intelligent targeting. Despite the challenges in mechanistic understanding and biosafety, future advancements through multiomics, intelligent nanosystems, and synergistic cell death pathways are anticipated to propel this field. This strategy indicates a possible transformation in anti-infective therapy from broad-spectrum killing to precision regulation. This shift offers a potentially effective solution to address drug-resistant bacterial infections.