Enzyme-Activated, Chemiluminescent Siderophore-Dioxetane Probes Enable the Selective and Highly Sensitive Detection of Bacterial Pathogens

Carsten Peukert, Sachin Popat Gholap, Ori Green, Lukas Pinkert, Joop van den Heuvel, Marco van Ham, Doron Shabat, Mark Brönstrup

Research output: Contribution to journalArticlepeer-review

Abstract

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 9.1×103 CFU mL−1 of S. aureus and 5.0×104 CFU mL−1 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.

Original languageEnglish
JournalAngewandte Chemie - International Edition
DOIs
StateAccepted/In press - 2022

Keywords

  • Bacterial Diagnostics
  • Chemiluminescence
  • Drug Delivery
  • Imaging
  • Siderophores

Fingerprint

Dive into the research topics of 'Enzyme-Activated, Chemiluminescent Siderophore-Dioxetane Probes Enable the Selective and Highly Sensitive Detection of Bacterial Pathogens'. Together they form a unique fingerprint.

Cite this