| Online-Ressource |
Verfasst von: | Loureiro, Ines [VerfasserIn]  |
| Faria, Joana [VerfasserIn]  |
| Clayton, Christine [VerfasserIn]  |
| Ribeiro, Sandra Macedo [VerfasserIn]  |
| Roy, Nilanjan [VerfasserIn]  |
| Santarém, Nuno [VerfasserIn]  |
| Tavares, Joana [VerfasserIn]  |
| Cordeiro-da-Silva, Anabela [VerfasserIn]  |
Titel: | Knockdown of asparagine synthetase A renders trypanosoma brucei auxotrophic to asparagine |
Verf.angabe: | Inês Loureiro, Joana Faria, Christine Clayton, Sandra Macedo Ribeiro, Nilanjan Roy, Nuno Santarém, Joana Tavares, Anabela Cordeiro-da-Silva |
E-Jahr: | 2013 |
Jahr: | December 5, 2013 |
Umfang: | 14 S. |
Teil: | volume:7 |
| year:2013 |
| number:12 |
| elocationid:e2578 |
| pages:1-14 |
| extent:14 |
Fussnoten: | Gesehen am 08.06.2021 |
Titel Quelle: | Enthalten in: Public Library of SciencePLoS neglected tropical diseases |
Ort Quelle: | Lawrence, Kan. : PLoS, 2007 |
Jahr Quelle: | 2013 |
Band/Heft Quelle: | 7(2013), 12, Artikel-ID e2578, Seite 1-14 |
ISSN Quelle: | 1935-2735 |
Abstract: | Asparagine synthetase (AS) catalyzes the ATP-dependent conversion of aspartate into asparagine using ammonia or glutamine as nitrogen source. There are two distinct types of AS, asparagine synthetase A (AS-A), known as strictly ammonia-dependent, and asparagine synthetase B (AS-B), which can use either ammonia or glutamine. The absence of AS-A in humans, and its presence in trypanosomes, suggested AS-A as a potential drug target that deserved further investigation. We report the presence of functional AS-A in Trypanosoma cruzi (TcAS-A) and Trypanosoma brucei (TbAS-A): the purified enzymes convert L-aspartate into L-asparagine in the presence of ATP, ammonia and Mg2+. TcAS-A and TbAS-A use preferentially ammonia as a nitrogen donor, but surprisingly, can also use glutamine, a characteristic so far never described for any AS-A. TbAS-A knockdown by RNAi didn't affect in vitro growth of bloodstream forms of the parasite. However, growth was significantly impaired when TbAS-A knockdown parasites were cultured in medium with reduced levels of asparagine. As expected, mice infections with induced and non-induced T. brucei RNAi clones were similar to those from wild-type parasites. However, when induced T. brucei RNAi clones were injected in mice undergoing asparaginase treatment, which depletes blood asparagine, the mice exhibited lower parasitemia and a prolonged survival in comparison to similarly-treated mice infected with control parasites. Our results show that TbAS-A can be important under in vivo conditions when asparagine is limiting, but is unlikely to be suitable as a drug target. |
DOI: | doi:10.1371/journal.pntd.0002578 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1371/journal.pntd.0002578 |
| Volltext: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002578 |
| DOI: https://doi.org/10.1371/journal.pntd.0002578 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Ammonia |
| Asparagine |
| Glutamine |
| Parasitic diseases |
| RNA interference |
| Trypanosoma |
| Trypanosoma brucei gambiense |
| Trypanosoma cruzi |
K10plus-PPN: | 1760029998 |
Verknüpfungen: | → Zeitschrift |
Knockdown of asparagine synthetase A renders trypanosoma brucei auxotrophic to asparagine / Loureiro, Ines [VerfasserIn]; December 5, 2013 (Online-Ressource)