Influence of ecto-nucleoside triphosphate diphosphohydrolase activity on trypanosoma cruzi infectivity and virulence.

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Autor(es): dc.creatorSantos, Ramon de Freitas-
Autor(es): dc.creatorPôssa, Marcela Auxiliadora Souza-
Autor(es): dc.creatorBastos, Matheus Silva e-
Autor(es): dc.creatorGuedes, Paulo Marcos da Matta-
Autor(es): dc.creatorAlmeida, Márcia Rogéria de-
Autor(es): dc.creatorDeMarco, Ricardo-
Autor(es): dc.creatorAlmeida, Sergio Verjovski-
Autor(es): dc.creatorBahia, Maria Terezinha-
Autor(es): dc.creatorFietto, Juliana Lopes Rangel-
Data de aceite: dc.date.accessioned2019-11-06T13:32:34Z-
Data de disponibilização: dc.date.available2019-11-06T13:32:34Z-
Data de envio: dc.date.issued2015-03-12-
Data de envio: dc.date.issued2015-03-12-
Data de envio: dc.date.issued2009-
Fonte completa do material: dc.identifierhttp://www.repositorio.ufop.br/handle/123456789/4609-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/557650-
Descrição: dc.descriptionBackground: The protozoan Trypanosoma cruzi is the causative agent of Chagas disease. There are no vaccines or effective treatment, especially in the chronic phase when most patients are diagnosed. There is a clear necessity to develop new drugs and strategies for the control and treatment of Chagas disease. Recent papers have suggested the ecto-nucleotidases (from CD39 family) from pathogenic agents as important virulence factors. In this study we evaluated the influence of Ecto- Nucleoside-Triphosphate-Diphosphohydrolase (Ecto-NTPDase) activity on infectivity and virulence of T. cruzi using both in vivo and in vitro models. Methodology/Principal Findings: We followed Ecto-NTPDase activities of Y strain infective forms (trypomastigotes) obtained during sequential sub-cultivation in mammalian cells. ATPase/ADPase activity ratios of cell-derived trypomastigotes decreased 3- to 6-fold and infectivity was substantially reduced during sequential sub-cultivation. Surprisingly, at third to fourth passages most of the cell-derived trypomastigotes could not penetrate mammalian cells and had differentiated into amastigote-like parasites that exhibited 3- to 4-fold lower levels of Ecto-NTPDase activities. To evidence the participation of T. cruzi Ecto-NTPDase1 in the infective process, we evaluated the effect of known Ecto- ATPDase inhibitors (ARL 67156, Gadolinium and Suramin), or anti-NTPDase-1 polyclonal antiserum on ATPase and ADPase hydrolytic activities in recombinant T. cruzi NTPDase-1 and in live trypomastigotes. All tests showed a partial inhibition of Ecto-ATPDase activities and a marked inhibition of trypomastigotes infectivity. Mice infections with Ecto-NTPDase-inhibited trypomastigotes produced lower levels of parasitemia and higher host survival than with non-inhibited control parasites. Conclusions/Significance: Our results suggest that Ecto-ATPDases act as facilitators of infection and virulence in vitro and in vivo and emerge as target candidates in chemotherapy of Chagas disease.-
Idioma: dc.languageen-
Direitos: dc.rightsNenhuma autorização é necessária para depósito dos artigos publicados pelos Periódicos PloS em repositório. Fonte: Plos <http://www.plos.org/open-access/> Acesso em: 14 nov. 2014.-
Título: dc.titleInfluence of ecto-nucleoside triphosphate diphosphohydrolase activity on trypanosoma cruzi infectivity and virulence.-
Aparece nas coleções:Repositório Institucional - UFOP

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