Department of Nephrology and Endocrinology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China.
Department of Nephrology, Beijing Key Laboratory for Immune-Mediated Inflammatory 9 Diseases, China-Japan Friendship Hospital, Beijing 100029, China.
Biomed Pharmacother. 2023 Jul;163:114859. doi: 10.1016/j.biopha.2023.114859. Epub 2023 May 9.
Uropathogenic Escherichia coli (UPEC) is the main pathogen of recurrent urinary tract infections (RUTIs). Urinary tract infection is a complicated interaction between UPEC and the host. During infection, UPEC can evade the host's immune response and retain in bladder epithelial cells, which requires adequate nutritional support. Iron is the first necessary trace element in life and a key nutritional factor, making it an important part of the competition between UPEC and the host. On the one hand, UPEC grabs iron to satisfy its reproduction, on the other hand, the host relies on iron to build nutritional immunity defenses against UPEC. Ferritinophagy is a selective autophagy of ferritin mediated by nuclear receptor coactivator 4, which is not only a way for the host to regulate iron metabolism to maintain iron homeostasis, but also a key point of competition between the host and UPEC. Although recent studies have confirmed the role of ferritinophagy in the progression of many diseases, the mechanism of potential interactions between ferritinophagy in UPEC and the host is poorly understood. In this paper, we reviewed the potential mechanisms of ferritinophagy-mediated iron competition in the UPEC-host interactions. This competitive relationship, like a tug-of-war, is a confrontation between the capability of UPEC to capture iron and the host's nutritional immunity defense, which could be the trigger for RUTIs. Therefore, understanding ferritinophagy-mediated iron competition may provide new strategies for exploring effective antibiotic alternative therapies to prevent and treat RUTIs.
尿路致病性大肠杆菌（UPEC）是复发性尿路感染（RUTI）的主要病原体。尿路感染是 UPEC 与宿主之间复杂的相互作用。在感染过程中，UPEC 可以逃避宿主的免疫反应并在膀胱上皮细胞中存活，这需要充足的营养支持。铁是生命中第一必需微量元素，也是关键的营养因素，因此它是 UPEC 和宿主之间竞争的重要组成部分。一方面，UPEC 抢夺铁以满足其繁殖需求，另一方面，宿主依赖铁来建立营养免疫防御以对抗 UPEC。铁蛋白自噬是核受体共激活因子 4 介导的铁蛋白选择性自噬，它不仅是宿主调节铁代谢以维持铁平衡的一种方式，也是宿主和 UPEC 之间竞争的关键点。尽管最近的研究证实了铁蛋白自噬在许多疾病进展中的作用，但铁蛋白自噬在 UPEC 和宿主之间的潜在相互作用机制尚不清楚。本文综述了 UPEC-宿主相互作用中铁蛋白自噬介导的铁竞争的潜在机制。这种竞争关系就像拔河比赛一样，是 UPEC 捕获铁的能力与宿主营养免疫防御之间的对抗，可能是 RUTI 的触发因素。因此，了解铁蛋白自噬介导的铁竞争可能为探索有效的抗生素替代疗法以预防和治疗 RUTI 提供新策略。
