Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway
Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron an...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/15/6/669 |
| _version_ | 1797483470337867776 |
|---|---|
| author | Anthony Marchand Joyce W. M. Van Bree Aya C. Taki Mati Moyat Gerardo Turcatti Marc Chambon Adam Alexander Thil Smith Rory Doolan Robin B. Gasser Nicola Laraine Harris Tiffany Bouchery |
| author_facet | Anthony Marchand Joyce W. M. Van Bree Aya C. Taki Mati Moyat Gerardo Turcatti Marc Chambon Adam Alexander Thil Smith Rory Doolan Robin B. Gasser Nicola Laraine Harris Tiffany Bouchery |
| author_sort | Anthony Marchand |
| collection | DOAJ |
| description | Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model <i>Nippostrongylus brasiliensis</i> (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms. |
| first_indexed | 2024-03-09T22:47:24Z |
| format | Article |
| id | doaj.art-69f540fd176149048aff41ba24ed53ce |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:47:24Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-69f540fd176149048aff41ba24ed53ce2023-11-23T18:26:43ZengMDPI AGPharmaceuticals1424-82472022-05-0115666910.3390/ph15060669Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding PathwayAnthony Marchand0Joyce W. M. Van Bree1Aya C. Taki2Mati Moyat3Gerardo Turcatti4Marc Chambon5Adam Alexander Thil Smith6Rory Doolan7Robin B. Gasser8Nicola Laraine Harris9Tiffany Bouchery10Laboratory of Intestinal Immunology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, SwitzerlandDepartment of Immunology and Pathology, Alfred Medical Research and Education Precinct (AMREP), Monash University, Melbourne, VIC 3004, AustraliaMelbourne Veterinary School, The University of Melbourne, Melbourne, VIC 3052, AustraliaLaboratory of Intestinal Immunology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, SwitzerlandBiomolecular Screening Facility, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, SwitzerlandBiomolecular Screening Facility, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, SwitzerlandMetabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, AustraliaHookworm Immuno-Biology Laboratory, Swiss Tropical and Public Health Institute, 4123 Allschwill, SwitzerlandMelbourne Veterinary School, The University of Melbourne, Melbourne, VIC 3052, AustraliaLaboratory of Intestinal Immunology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, SwitzerlandLaboratory of Intestinal Immunology, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, SwitzerlandHookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model <i>Nippostrongylus brasiliensis</i> (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms.https://www.mdpi.com/1424-8247/15/6/669drug-screeninghelminthhookwormblood-feedingviabilityfluorescence |
| spellingShingle | Anthony Marchand Joyce W. M. Van Bree Aya C. Taki Mati Moyat Gerardo Turcatti Marc Chambon Adam Alexander Thil Smith Rory Doolan Robin B. Gasser Nicola Laraine Harris Tiffany Bouchery Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway Pharmaceuticals drug-screening helminth hookworm blood-feeding viability fluorescence |
| title | Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway |
| title_full | Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway |
| title_fullStr | Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway |
| title_full_unstemmed | Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway |
| title_short | Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway |
| title_sort | novel high throughput fluorescence based assay for the identification of nematocidal compounds that target the blood feeding pathway |
| topic | drug-screening helminth hookworm blood-feeding viability fluorescence |
| url | https://www.mdpi.com/1424-8247/15/6/669 |
| work_keys_str_mv | AT anthonymarchand novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway AT joycewmvanbree novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway AT ayactaki novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway AT matimoyat novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway AT gerardoturcatti novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway AT marcchambon novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway AT adamalexanderthilsmith novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway AT rorydoolan novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway AT robinbgasser novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway AT nicolalaraineharris novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway AT tiffanybouchery novelhighthroughputfluorescencebasedassayfortheidentificationofnematocidalcompoundsthattargetthebloodfeedingpathway |