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

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...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2022-06, Vol.61 (25), p.e202201423-n/a
Main Authors: Peukert, Carsten, Popat Gholap, Sachin, Green, Ori, Pinkert, Lukas, Heuvel, Joop, Ham, Marco, Shabat, Doron, Brönstrup, Mark
Format: Article
Language:English
Subjects:
Bacteria
Bacterial Diagnostics
Bacterial diseases
Chemiluminescence
Conjugates
Deferoxamine
Drug Delivery
Epithelial cells
Epithelium
Fluorescent indicators
Imaging
Iron
Pathogens
Probes
Pseudomonas aeruginosa
Siderophores
Staphylococcus aureus
Transportation systems
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Summary: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. A sensitive diagnosis is crucial for the successful treatment of bacterial infections. The conjugation of bacteria‐specific, uptake‐enhancing siderophore vectors with enzyme‐inducible chemiluminescent dioxetanes enabled the broad‐spectrum detection of “ESKAPE” pathogens. The probes displayed a high sensitivity in human plasma and also detected intracellular Gram‐positive and ‐negative bacteria.
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202201423