Host-Directed Ferroptotic Stress Modulation Against Intracellular Bacterial Infections: Mechanisms, Evidence, and Translational Challenges.

Authors

Youle Zheng, Jin Feng, Qinyuan Chang, Tong Wang, Qianwei Qu, Yanhua Li

Published in

Medicinal research reviews. Nov 13, 2026. Epub Nov 13, 2026.

Abstract

The rise in antibiotic resistance and the persistence of intracellular infections underscore the urgent need for novel antimicrobial agents and strategies. Ferroptotic stress is a cell state marked by transiently elevated Fe²⁺ levels, increased lipid peroxidation, and altered redox balance. It has gained significant attention due to its role in the progression of various diseases, especially bacterial infections. By inducing intracellular iron overload, disrupting the bacterial microenvironment, and activating innate immune cells like macrophages, it serves as a crucial strategy to restrict intracellular bacterial growth and limit the emergence of resistance. Despite growing interest, systematic reviews integrating host ferroptotic stress modulation with precision antimicrobial strategies remain scarce. This review explores recent advancements in host-directed ferroptotic stress strategies for combating bacterial infections, focusing on metabolic reprogramming, macrophage-mediated defense, membrane remodeling, nutrient deprivation, iron trafficking, direct bacteriolysis, and antibiotic synergism. It highlights the potential of precision modulation of host ferroptotic stress to enhance antimicrobial strategies and identifies key research gaps to advance related therapeutic approaches.

PMID:
43031379
Bibliographic data and abstract were imported from PubMed on 14 Nov 2026.

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