Department of Chemical Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Braunschweig, Germany.
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.
Angew Chem Int Ed Engl. 2022 Jun 20;61(25):e202201423. doi: 10.1002/anie.202201423. Epub 2022 Apr 27.
The sensitive detection of bacterial infections is a prerequisite for their successful treatment. The use of a chemiluminescent readout was so far hampered by an insufficient probe enrichment at the pathogens. We coupled siderophore moieties, that harness the unique iron transport system of bacteria, with enzyme-activatable dioxetanes and obtained seven trifunctional probes with high signal-to-background ratios (S/B=426-859). Conjugates with efficient iron transport capability into bacteria were identified through a growth recovery assay. All ESKAPE pathogens were labelled brightly by desferrioxamine conjugates, while catechols were weaker due to self-quenching. Bacteria could also be detected inside lung epithelial cells. The best probe 8 detected 9.1×10 CFU mL of S. aureus and 5.0×10 CFU mL of P. aeruginosa, while the analogous fluorescent probe 10 was 205-305fold less sensitive. This qualifies siderophore dioxetane probes for the selective and sensitive detection of bacteria.
细菌感染的敏感检测是成功治疗的前提。化学发光读出法的应用迄今为止受到病原体中探针富集不足的阻碍。我们将铁载体部分与酶激活的二氧杂环丁烷偶联，并获得了七种具有高信号背景比（S/B=426-859）的三功能探针。通过生长恢复测定鉴定了具有高效铁转运能力进入细菌的缀合物。所有 ESKAPE 病原体均被去铁胺缀合物明亮标记，而儿茶酚由于自猝灭而较弱。细菌也可以在肺上皮细胞内检测到。最佳探针 8 检测到 9.1×10 CFU/mL 的金黄色葡萄球菌和 5.0×10 CFU/mL 的铜绿假单胞菌，而类似的荧光探针 10 的灵敏度低 205-305 倍。这使铁载体二氧杂环丁烷探针有资格用于细菌的选择性和敏感检测。
