Multi-step strategies for synergistic treatment of urinary tract infections based on D-xylose-decorated antimicrobial peptide carbon dots

Chunhui Miao; Yajie Zhang; Guowen Liu; Jianming Yang; Kaiyuan Yu; Junqiang Lv; Ran Liu; Zhi Yao; Yuanjie Niu; Xiaojuan Wang; Quan Wang

doi:10.1016/j.biomaterials.2024.122547

Multi-step strategies for synergistic treatment of urinary tract infections based on D-xylose-decorated antimicrobial peptide carbon dots

Biomaterials. 2024 Mar 22:308:122547. doi: 10.1016/j.biomaterials.2024.122547. Online ahead of print.

Authors

Chunhui Miao¹, Yajie Zhang¹, Guowen Liu¹, Jianming Yang¹, Kaiyuan Yu¹, Junqiang Lv¹, Ran Liu¹, Zhi Yao¹, Yuanjie Niu², Xiaojuan Wang³, Quan Wang⁴

Affiliations

¹ Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
² The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 300211, China; Tianjin Key Laboratory of Precision Medicine for Sex Hormones and Diseases (in Preparation), Tianjin, 300211, China. Electronic address: niuyuanjie9317@163.com.
³ The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 300211, China; Tianjin Key Laboratory of Precision Medicine for Sex Hormones and Diseases (in Preparation), Tianjin, 300211, China. Electronic address: xjwang@tmu.edu.cn.
⁴ Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China; The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 300211, China; Tianjin Key Laboratory of Precision Medicine for Sex Hormones and Diseases (in Preparation), Tianjin, 300211, China. Electronic address: wangquan@tmu.edu.cn.

PMID: 38537344
DOI: 10.1016/j.biomaterials.2024.122547

Abstract

Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC), often reoccur due to the formation of intracellular bacterial colonies (IBCs) and antibiotic resistance. Given the significance of YadC for UPEC infection in our previous study, we developed D-xylose-decorated ɛ-poly-L-lysine (εPL)-based carbon dots (D-xyl@εPLCDs) that can be traced, and employed multi-step approaches to elucidate the functional roles of D-xyl@εPLCDs in UPEC infection. Compared to undecorated particles, D-xyl@εPLCDs demonstrate YadC-dependent bacterial targeting and exhibit enhanced bactericidal activities both intracellularly and extracellularly. Moreover, pre-treatment of D-xyl@εPLCDs before infection blocked the subsequent adhesion and invasion of UPEC to bladder epithelial cells 5637. Increase of ROS production and innate immune responses were observed in bladder epithelial cells 5637 treated with D-xyl@εPLCDs. In addition, treatment of D-xyl@εPLCDs post-infection facilitated clearance of UPEC in the bladders of the UTI mouse model, and reduced ultimate number of neutrophils, macrophages and inflammatory responses raised by invaded bacteria. Collectively, we presented a comprehensive evaluating system to show that D-xyl@εPLCDs exhibits superior bactericidal effects against UPEC, making them a promising candidate for drug development in clinical UTI therapeutics.

Keywords: Carbon dots; D-xylose; Intracellular bacteria; ɛ-poly-L-lysine.