Academic Journal
Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets
| العنوان: | Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets |
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| المؤلفون: | Curran, David M, Grote, Alexandra, Nursimulu, Nirvana, Geber, Adam, Voronin, Dennis, Jones, Drew R, Ghedin, Elodie, Parkinson, John |
| المساهمون: | National Institutes of Health, Natural Sciences and Engineering Research Council of Canada, Hospital for Sick Children Research Training Centre, Ruth L Kirschstein Institutional National Research Service, Ruth L Kirschstein Pre-doctoral Individual NRSA |
| المصدر: | eLife ; volume 9 ; ISSN 2050-084X |
| بيانات النشر: | eLife Sciences Publications, Ltd |
| سنة النشر: | 2020 |
| المجموعة: | eLife (E-Journal - via CrossRef) |
| الوصف: | The filarial nematode Brugia malayi represents a leading cause of disability in the developing world, causing lymphatic filariasis in nearly 40 million people. Currently available drugs are not well-suited to mass drug administration efforts, so new treatments are urgently required. One potential vulnerability is the endosymbiotic bacteria Wolbachia —present in many filariae—which is vital to the worm. Genome scale metabolic networks have been used to study prokaryotes and protists and have proven valuable in identifying therapeutic targets, but have only been applied to multicellular eukaryotic organisms more recently. Here, we present i DC625, the first compartmentalized metabolic model of a parasitic worm. We used this model to show how metabolic pathway usage allows the worm to adapt to different environments, and predict a set of 102 reactions essential to the survival of B. malayi . We validated three of those reactions with drug tests and demonstrated novel antifilarial properties for all three compounds. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.7554/elife.51850 |
| الاتاحة: | http://dx.doi.org/10.7554/elife.51850 https://cdn.elifesciences.org/articles/51850/elife-51850-v1.pdf https://cdn.elifesciences.org/articles/51850/elife-51850-v1.xml https://elifesciences.org/articles/51850 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.C3964446 |
| قاعدة البيانات: | BASE |
| DOI: | 10.7554/elife.51850 |
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