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Angew. Chem.-Int. Edit., Feb 06 2024, | https://doi.org/10.1002/anie.202319690
Breaking Iron Homeostasis: Iron Capturing Nanocomposites for Combating Bacterial Biofilm
Wenyue Sun 1, Jiao Sun 2, Qihang Ding 3, Manlin Qi 1, Jing Zhou 1, Yujia Shi 1, Jia Liu 1, Miae Won 3, Xiaolin Sun 1, Xue Bai 4, Biao Dong 4, Jong Seung Kim 5, Lin Wang 1
1Jilin University, Department of Oral Implantology, CHINA.
2Jilin University, Department of Cell Biology, CHINA.
3Korea University, Department of Chemistry, KOREA, REPUBLIC OF.
4Jilin University, College of Electronic Science and Engineering, CHINA.
5Korea University, Department of Chemistry, Anamdong, 02841, Seoul, KOREA, REPUBLIC OF.
CORRESPONDING AUTHOR : Jong Seung Kim
Abstract
Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal-organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a "give and take" approach for Ga3+/Fe3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application.
논문정보
- Research article
- 2024년 02월 (BRIC 등록일 2024-02-23)
- 국내(교신)+국외 연구진
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