Next Generation Chemiluminescent Probes for Antimalarial Drug Discovery
Malaria is caused by parasites of the Plasmodium genus and remains one of the most pressing human health problems. The spread of parasites resistant to or partially resistant to single or multiple drugs, including frontline antimalarial artemisinin and its derivatives, poses a serious threat to current and future malaria control efforts. In vitro drug assays are important for identifying new antimalarial compounds and monitoring drug resistance. Due to its robustness and ease of use, the [3H]-hypoxanthine incorporation assay is still considered a gold standard and is widely applied, despite limited sensitivity and the dependence on radioactive material. Here, we present a first-of-its-kind chemiluminescence-based antimalarial drug screening assay. The effect of compounds on P. falciparum is monitored by using a dioxetane-based substrate (AquaSpark β-D-galactoside) that emits high-intensity luminescence upon removal of a protective group (β-D-galactoside) by a transgenic β-galactosidase reporter enzyme. This biosensor enables highly sensitive, robust, and cost-effective detection of asexual, intraerythrocytic P. falciparum parasites without the need for parasite enrichment, washing, or purification steps. We are convinced that the ultralow detection limit of less than 100 parasites of the presented biosensor system will become instrumental in malaria research, including but not limited to drug screening.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
ACS infectious diseases - 10(2024), 4 vom: 12. Apr., Seite 1286-1297 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hellingman, Angela [VerfasserIn] |
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| Links: |
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| Themen: |
Antimalarials |
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| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 25.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acsinfecdis.3c00707 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370464931 |
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| 520 | |a Malaria is caused by parasites of the Plasmodium genus and remains one of the most pressing human health problems. The spread of parasites resistant to or partially resistant to single or multiple drugs, including frontline antimalarial artemisinin and its derivatives, poses a serious threat to current and future malaria control efforts. In vitro drug assays are important for identifying new antimalarial compounds and monitoring drug resistance. Due to its robustness and ease of use, the [3H]-hypoxanthine incorporation assay is still considered a gold standard and is widely applied, despite limited sensitivity and the dependence on radioactive material. Here, we present a first-of-its-kind chemiluminescence-based antimalarial drug screening assay. The effect of compounds on P. falciparum is monitored by using a dioxetane-based substrate (AquaSpark β-D-galactoside) that emits high-intensity luminescence upon removal of a protective group (β-D-galactoside) by a transgenic β-galactosidase reporter enzyme. This biosensor enables highly sensitive, robust, and cost-effective detection of asexual, intraerythrocytic P. falciparum parasites without the need for parasite enrichment, washing, or purification steps. We are convinced that the ultralow detection limit of less than 100 parasites of the presented biosensor system will become instrumental in malaria research, including but not limited to drug screening | ||
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| 700 | 1 | |a Buser, Tamara |e verfasserin |4 aut | |
| 700 | 1 | |a Thommen, Basil T |e verfasserin |4 aut | |
| 700 | 1 | |a Walz, Annabelle |e verfasserin |4 aut | |
| 700 | 1 | |a Passecker, Armin |e verfasserin |4 aut | |
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| 700 | 1 | |a Wittlin, Sergio |e verfasserin |4 aut | |
| 700 | 1 | |a Witmer, Kathrin |e verfasserin |4 aut | |
| 700 | 1 | |a Brancucci, Nicolas M B |e verfasserin |4 aut | |
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