细菌铁离子摄取系统与宿主抗感染免疫研究 进展
Recent Advances in Bacterial Iron Uptake Systems and Host Anti-Infective Immunity
DOI: 10.12677/acm.2026.1631009, PDF,   
作者: 蒋 珊, 钟雯婕*, 高 翔*：重庆医科大学附属口腔医院，重庆；口腔疾病研究重庆市重点实验室，重庆；口腔生物医学工程重庆市高校市级重点实验室，重庆
关键词: 细菌感染；铁离子稳态；调控机制；Bacterial Infection； Iron Homeostasis； Regulatory Mechanism
摘要: 细菌具有嗜铁性，细菌入侵后与宿主争夺的核心营养元素铁，而宿主可通过抑制对细菌对铁的摄取从而降低细菌感染。深入探究细菌与宿主之间如何获取铁资源、宿主如何通过调节铁代谢以增强抗感染能力，对细菌感染性疾病的防治具有重要意义。本文旨在综述细菌铁摄取途径与宿主铁代谢调控机制在感染过程中的相互作用，以期为通过靶向铁代谢提升宿主免疫力、防控细菌感染提供理论依据。
Abstract: It is well known that bacteria exhibit iron-loving properties. Upon invasion, bacteria compete with the host for iron, a core nutrient. The host can reduce bacterial infection by inhibiting bacterial iron uptake. Deepening our understanding of how bacteria and hosts acquire iron resources, and how the host enhances anti-infection capacity by regulating iron metabolism, holds significant implications for the prevention and treatment of bacterial infectious diseases. This review aims to summarize the interactions between bacterial iron uptake pathways and host iron metabolism regulatory mechanisms during infection, with the goal of providing theoretical foundations for enhancing host immunity and preventing bacterial infections through targeted iron metabolism modulation.
文章引用：蒋珊, 钟雯婕, 高翔. 细菌铁离子摄取系统与宿主抗感染免疫研究 进展[J]. 临床医学进展, 2026, 16(3): 2163-2173. https://doi.org/10.12677/acm.2026.1631009

参考文献

[1] Bullen, J.J. and Griffiths, E. (1999) Iron and Infection. Molecular, Physiological and Clinical Aspects, 10, S30-S34.
[2] Braun, V. (2001) Iron Uptake Mechanisms and Their Regulation in Pathogenic Bacteria. International Journal of Medical Microbiology, 291, 67-79. [Google Scholar] [CrossRef] [PubMed]
[3] Sun, W., Sun, J., Ding, Q., Qi, M., Zhou, J., Shi, Y., et al. (2024) Breaking Iron Homeostasis: Iron Capturing Nanocomposites for Combating Bacterial Biofilm. Angewandte Chemie, 136, e202319690. [Google Scholar] [CrossRef] 
[4] Tullius, M.V., Harmston, C.A., Owens, C.P., Chim, N., Morse, R.P., McMath, L.M., et al. (2011) Discovery and Characterization of a Unique Mycobacterial Heme Acquisition System. Proceedings of the National Academy of Sciences, 108, 5051-5056. [Google Scholar] [CrossRef] [PubMed]
[5] Pilpa, R.M., Robson, S.A., Villareal, V.A., Wong, M.L., Phillips, M. and Clubb, R.T. (2009) Functionally Distinct NEAT (Near Transporter) Domains within the Staphylococcus aureus IsdH/HarA Protein Extract Heme from Methemoglobin. Journal of Biological Chemistry, 284, 1166-1176. [Google Scholar] [CrossRef] [PubMed]
[6] Gat, O., Zaide, G., Inbar, I., Grosfeld, H., Chitlaru, T., Levy, H., et al. (2008) Characterization of Bacillus anthracis Iron-Regulated Surface Determinant (Isd) Proteins Containing NEAT Domains. Molecular Microbiology, 70, 983-999. [Google Scholar] [CrossRef] [PubMed]
[7] Choby, J.E. and Skaar, E.P. (2016) Heme Synthesis and Acquisition in Bacterial Pathogens. Journal of Molecular Biology, 428, 3408-3428. [Google Scholar] [CrossRef] [PubMed]
[8] Kuang, H., Dou, G., Cheng, L., Wang, X., Xu, H., Liu, X., et al. (2023) Humoral Regulation of Iron Metabolism by Extracellular Vesicles Drives Antibacterial Response. Nature Metabolism, 5, 111-128. [Google Scholar] [CrossRef] [PubMed]
[9] Skaar, E.P., Humayun, M., Bae, T., DeBord, K.L. and Schneewind, O. (2004) Iron-Source Preference of Staphylococcus aureus Infections. Science, 305, 1626-1628. [Google Scholar] [CrossRef] [PubMed]
[10] Tong, Y. and Guo, M. (2008) Bacterial Heme-Transport Proteins and Their Heme-Coordination Modes. Archives of Biochemistry and Biophysics, 481, 1-15. [Google Scholar] [CrossRef] [PubMed]
[11] Klebba, P.E., Newton, S.M.C., Six, D.A., Kumar, A., Yang, T., Nairn, B.L., et al. (2021) Iron Acquisition Systems of Gram-Negative Bacterial Pathogens Define TonB-Dependent Pathways to Novel Antibiotics. Chemical Reviews, 121, 5193-5239. [Google Scholar] [CrossRef] [PubMed]
[12] Mietzner, T.A., Tencza, S.B., Adhikari, P., Vaughan, K.G. and Nowalk, A.J. (1998) Fe(III) Periplasm-to-Cytosol Transporters of Gram-Negative Pathogens. In: Current Topics in Microbiology and Immunology, Springer, 113-135. [Google Scholar] [CrossRef] [PubMed]
[13] Raffatellu, M., George, M.D., Akiyama, Y., Hornsby, M.J., Nuccio, S., Paixao, T.A., et al. (2009) Lipocalin-2 Resistance Confers an Advantage to Salmonella Enterica Serotype Typhimurium for Growth and Survival in the Inflamed Intestine. Cell Host & Microbe, 5, 476-486. [Google Scholar] [CrossRef] [PubMed]
[14] Behnsen, J., Jellbauer, S., Wong, C.P., Edwards, R.A., George, M.D., Ouyang, W., et al. (2014) The Cytokine IL-22 Promotes Pathogen Colonization by Suppressing Related Commensal Bacteria. Immunity, 40, 262-273. [Google Scholar] [CrossRef] [PubMed]
[15] Spiga, L., Fansler, R.T., Perera, Y.R., Shealy, N.G., Munneke, M.J., David, H.E., et al. (2023) Iron Acquisition by a Commensal Bacterium Modifies Host Nutritional Immunity during Salmonella Infection. Cell Host & Microbe, 31, 1639-1654.e10. [Google Scholar] [CrossRef] [PubMed]
[16] Schryvers, A.B. (2022) Targeting Bacterial Transferrin and Lactoferrin Receptors for Vaccines. Trends in Microbiology, 30, 820-830. [Google Scholar] [CrossRef] [PubMed]
[17] Hammer, N.D. and Skaar, E.P. (2011) Molecular Mechanisms of Staphylococcus aureus Iron Acquisition. Annual Review of Microbiology, 65, 129-147. [Google Scholar] [CrossRef] [PubMed]
[18] Perry, R.D., Bobrov, A.G., Kirillina, O., Rhodes, E.R., Actis, L.A. and Fetherston, J.D. (2012) Yersinia Pestis Transition Metal Divalent Cation Transporters. In: Advances in Experimental Medicine and Biology, Springer, 267-279. [Google Scholar] [CrossRef] [PubMed]
[19] Sepúlveda Cisternas, I., Salazar, J.C. and García-Angulo, V.A. (2018) Overview on the Bacterial Iron-Riboflavin Metabolic Axis. Frontiers in Microbiology, 9, Article 1478. [Google Scholar] [CrossRef] [PubMed]
[20] (2023) Pathogenic Bacteria Build an Iron-Storage System for Growth and Survival in Their Hosts. Nature.
https://www.nature.com/articles/d41586-023-03367-x
[21] Nairz, M. and Weiss, G. (2020) Iron in Infection and Immunity. Molecular Aspects of Medicine, 75, Article 100864. [Google Scholar] [CrossRef] [PubMed]
[22] Toyofuku, M., Schild, S., Kaparakis-Liaskos, M. and Eberl, L. (2023) Composition and Functions of Bacterial Membrane Vesicles. Nature Reviews Microbiology, 21, 415-430. [Google Scholar] [CrossRef] [PubMed]
[23] Wang, M., Nie, Y. and Wu, X. (2020) Extracellular Heme Recycling and Sharing across Species by Novel Mycomembrane Vesicles of a Gram-Positive Bacterium. The ISME Journal, 15, 605-617. [Google Scholar] [CrossRef] [PubMed]
[24] Flo, T.H., Smith, K.D., Sato, S., Rodriguez, D.J., Holmes, M.A., Strong, R.K., et al. (2004) Lipocalin 2 Mediates an Innate Immune Response to Bacterial Infection by Sequestrating Iron. Nature, 432, 917-921. [Google Scholar] [CrossRef] [PubMed]
[25] Soe-Lin, S., Apte, S.S., Andriopoulos, B., Andrews, M.C., Schranzhofer, M., Kahawita, T., et al. (2009) Nramp1 Promotes Efficient Macrophage Recycling of Iron Following Erythrophagocytosis in Vivo. Proceedings of the National Academy of Sciences, 106, 5960-5965. [Google Scholar] [CrossRef] [PubMed]
[26] Cellier, M.F., Courville, P. and Campion, C. (2007) Nramp1 Phagocyte Intracellular Metal Withdrawal Defense. Microbes and Infection, 9, 1662-1670. [Google Scholar] [CrossRef] [PubMed]
[27] Li, Y., Qu, G., Dou, G., Ren, L., Dang, M., Kuang, H., et al. (2024) Engineered Extracellular Vesicles Driven by Erythrocytes Ameliorate Bacterial Sepsis by Iron Recycling, Toxin Clearing and Inflammation Regulation. Advanced Science, 11, e2306884. [Google Scholar] [CrossRef] [PubMed]
[28] Horino, T., Matsumoto, T., Uramatsu, M., Tanabe, M., Tateda, K., Miyazaki, S., et al. (2005) Interleukin-1-Deficient Mice Exhibit High Sensitivity to Gut-Derived Sepsis Caused by Pseudomonas Aeruginosa. Cytokine, 30, 339-346. [Google Scholar] [CrossRef] [PubMed]
[29] Liu, Z., Reba, S., Chen, D.W., et al. (2014) Regulation of Mammalian Siderophore 2,5-DHBA in the Innate Immune Response to Infection 2,5-DHBA Augments Bacterial Growth. Journal of Experimental Medicine, 211, 1197-1213. [Google Scholar] [CrossRef] [PubMed]
[30] Singh, P.K., Parsek, M.R., Greenberg, E.P. and Welsh, M.J. (2002) A Component of Innate Immunity Prevents Bacterial Biofilm Development. Nature, 417, 552-555. [Google Scholar] [CrossRef] [PubMed]
[31] Mayneris-Perxachs, J., Moreno-Navarrete, J.M. and Fernández-Real, J.M. (2022) The Role of Iron in Host-Microbiota Crosstalk and Its Effects on Systemic Glucose Metabolism. Nature Reviews Endocrinology, 18, 683-698. [Google Scholar] [CrossRef] [PubMed]
[32] Ganz, T. and Nemeth, E. (2015) Iron Homeostasis in Host Defence and Inflammation. Nature Reviews Immunology, 15, 500-510. [Google Scholar] [CrossRef] [PubMed]
[33] Tuomeinen, T.P., Aregbesoia, A., Virtanen, J.K., et al. (2015) Serum Hepcidin Concentrations and Type 2 Diabetes. World Journal of Diabetes, 6, 978-982.
[34] Fabián, M.S., María, M., Alejandra, A., et al. (2015) Circulating Hepcidin in Type 2 Diabetes: A Multivariate Analysis and Double Blind Evaluation of Metformin Effects. Molecular Nutrition & Food Research, 59, 2460-2470. [Google Scholar] [CrossRef] [PubMed]
[35] Yang, Y., Wang, Y., Guo, L., Gao, W., Tang, T. and Yan, M. (2022) Interaction between Macrophages and Ferroptosis. Cell Death & Disease, 13, Article No. 355. [Google Scholar] [CrossRef] [PubMed]
[36] Deng, D.K., Zhang, J.J., Gan, D., et al. (2022) Roles of Extracellular Vesicles in Periodontal Homeostasis and Their Therapeutic Potential. Journal of Nanobiotechnology, 20, Article No. 545. [Google Scholar] [CrossRef] [PubMed]
[37] Huang, W. and Wilks, A. (2017) Extracellular Heme Uptake and the Challenge of Bacterial Cell Membranes. Annual Review of Biochemistry, 86, 799-823. [Google Scholar] [CrossRef] [PubMed]
[38] Patras, K.A., Ha, A.D., Rooholfada, E., Olson, J., Ramachandra Rao, S.P., Lin, A.E., et al. (2019) Augmentation of Urinary Lactoferrin Enhances Host Innate Immune Clearance of Uropathogenic Escherichia coli. Journal of Innate Immunity, 11, 481-495. [Google Scholar] [CrossRef] [PubMed]
[39] Hendricks, M.R., Lane, S., Melvin, J.A., Ouyang, Y., Stolz, D.B., Williams, J.V., et al. (2021) Extracellular Vesicles Promote Transkingdom Nutrient Transfer during Viral-Bacterial Co-Infection. Cell Reports, 34, Article 108672. [Google Scholar] [CrossRef] [PubMed]
[40] Keller, M.D., Ching, K.L., Liang, F., Dhabaria, A., Tam, K., Ueberheide, B.M., et al. (2020) Decoy Exosomes Provide Protection against Bacterial Toxins. Nature, 579, 260-264. [Google Scholar] [CrossRef] [PubMed]
[41] Sun, Q., Yang, J., Zhang, M., Zhang, Y., Ma, H., Tran, N.T., et al. (2023) Exosomes Drive Ferroptosis by Stimulating Iron Accumulation to Inhibit Bacterial Infection in Crustaceans. Journal of Biological Chemistry, 299, Article 105463. [Google Scholar] [CrossRef] [PubMed]

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