Drug Research Program, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia.
Chembiochem. 2024 Jan 15;25(2):e202300638. doi: 10.1002/cbic.202300638. Epub 2023 Nov 27.
This study aimed to identify inhibitors of the translocated intimin receptor (Tir) of enteropathogenic Escherichia coli (EPEC). EPEC is an intestinal pathogen that causes diarrhea and is a major health concern worldwide. Because Tir is a key virulence factor involved in EPEC pathogenesis, inhibiting its function is a potential strategy for controlling EPEC infections. Virtual screening was applied to chemical libraries to search for compounds that inhibit Tir-mediated bacterial adherence to host cells. Three sites were targeted using the cocrystal structure published earlier. A selection of compounds was then assessed in a cell-based infection model and fluorescence microscopy assay. The results of this study provide a basis for further optimization and testing of Tir inhibitors as potential therapeutic agents for EPEC infections.
本研究旨在鉴定肠致病性大肠杆菌（EPEC）转位内膜受体（Tir）的抑制剂。EPEC 是一种肠道病原体，可引起腹泻，是全球关注的主要健康问题。由于 Tir 是参与 EPEC 发病机制的关键毒力因子，抑制其功能是控制 EPEC 感染的一种潜在策略。本研究采用虚拟筛选技术，从化学文库中搜索抑制 Tir 介导的细菌与宿主细胞黏附的化合物。使用之前发表的共晶结构靶向三个位点。然后，在基于细胞的感染模型和荧光显微镜检测中评估了一组化合物。本研究结果为进一步优化和测试 Tir 抑制剂作为 EPEC 感染的潜在治疗剂提供了基础。
