Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10216/118204
Autor(es): | Faria, J Loureiro, I Santarém, N Macedo-Ribeiro, S Tavares, J Cordeiro-da-Silva, A |
Título: | Leishmania infantum Asparagine Synthetase A Is Dispensable for Parasites Survival and Infectivity |
Editor: | Public Library of Science |
Data de publicação: | 2016 |
Resumo: | A growing interest in asparagine (Asn) metabolism has currently been observed in cancer and infection fields. Asparagine synthetase (AS) is responsible for the conversion of aspartate into Asn in an ATP-dependent manner, using ammonia or glutamine as a nitrogen source. There are two structurally distinct AS: the strictly ammonia dependent, type A, and the type B, which preferably uses glutamine. Absent in humans and present in trypanosomatids, AS-A was worthy of exploring as a potential drug target candidate. Appealingly, it was reported that AS-A was essential in Leishmania donovani, making it a promising drug target. In the work herein we demonstrate that Leishmania infantum AS-A, similarly to Trypanosoma spp. and L. donovani, is able to use both ammonia and glutamine as nitrogen donors. Moreover, we have successfully generated LiASA null mutants by targeted gene replacement in L. infantum, and these parasites do not display any significant growth or infectivity defect. Indeed, a severe impairment of in vitro growth was only observed when null mutants were cultured in asparagine limiting conditions. Altogether our results demonstrate that despite being important under asparagine limitation, LiAS-A is not essential for parasite survival, growth or infectivity in normal in vitro and in vivo conditions. Therefore we exclude AS-A as a suitable drug target against L. infantum parasites. |
URI: | https://repositorio-aberto.up.pt/handle/10216/118204 |
Fonte: | PLoS Neglected Tropical Diseases, vol.10(1):e0004365 |
Informação Relacionada: | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F79712%2F2011/PT info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F64528%2F2009/PT |
Tipo de Documento: | Artigo em Revista Científica Internacional |
Condições de Acesso: | openAccess |
Licença: | https://creativecommons.org/licenses/by/4.0/ |
Aparece nas coleções: | I3S - Artigo em Revista Científica Internacional |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Faria et al_PLOSNTD_2016.pdf | 2.42 MB | Adobe PDF | Ver/Abrir |
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