Influence of ecto-nucleoside triphosphate diphosphohydrolase activity on Trypanosoma cruzi infectivity and virulence.
| dc.contributor.author | Santos, Ramon de Freitas | |
| dc.contributor.author | Pôssa, Marcela Auxiliadora Souza | |
| dc.contributor.author | Bastos, Matheus Silva e | |
| dc.contributor.author | Guedes, Paulo Marcos da Matta | |
| dc.contributor.author | Almeida, Márcia Rogéria de | |
| dc.contributor.author | DeMarco, Ricardo | |
| dc.contributor.author | Almeida, Sergio Verjovski | |
| dc.contributor.author | Bahia, Maria Terezinha | |
| dc.contributor.author | Fietto, Juliana Lopes Rangel | |
| dc.date.accessioned | 2015-03-12T18:51:36Z | |
| dc.date.available | 2015-03-12T18:51:36Z | |
| dc.date.issued | 2009 | |
| dc.description.abstract | Background: 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. | pt_BR |
| dc.identifier.citation | SANTOS, R. de F. et al. Influence of ecto-nucleoside triphosphate diphosphohydrolase activity on Trypanosoma cruzi infectivity and virulence. PLoS Neglected Tropical Diseases, v. 3, p. e387, 2009. Disponível em: <http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000387>. Acesso em: 08 nov. 2014. | pt_BR |
| dc.identifier.doi | https://doi.org/10.1371/journal.pntd.0000387 | |
| dc.identifier.issn | 1932-6203 | |
| dc.identifier.uri | http://www.repositorio.ufop.br/handle/123456789/4609 | |
| dc.language.iso | en_US | pt_BR |
| dc.rights.license | Os trabalhos publicados na Plos one estão sob Licença Creative Commons que permite copiar, distribuir e transmitir o trabalho, desde que sejam citados o autor e licenciante. Não permite o uso para fins comerciais nem a adaptação. Fonte: Plos one <https://www.plos.org/open-access>. Acesso em: 03 jan. 2017. | pt_BR |
| dc.title | Influence of ecto-nucleoside triphosphate diphosphohydrolase activity on Trypanosoma cruzi infectivity and virulence. | pt_BR |
| dc.type | Artigo publicado em periodico | pt_BR |