Navigation überspringen
Universitätsbibliothek Heidelberg
Status: Bibliographieeintrag

Verfügbarkeit
Standort: ---
Exemplare: ---
heiBIB
 Online-Ressource
Verfasst von:Loureiro, Ines [VerfasserIn]   i
 Faria, Joana [VerfasserIn]   i
 Clayton, Christine [VerfasserIn]   i
 Ribeiro, Sandra Macedo [VerfasserIn]   i
 Roy, Nilanjan [VerfasserIn]   i
 Santarém, Nuno [VerfasserIn]   i
 Tavares, Joana [VerfasserIn]   i
 Cordeiro-da-Silva, Anabela [VerfasserIn]   i
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

Permanenter Link auf diesen Titel (bookmarkfähig):  https://katalog.ub.uni-heidelberg.de/titel/68745905   QR-Code
zum Seitenanfang