Santos, Ramon de FreitasPôssa, Marcela Auxiliadora SouzaBastos, Matheus Silva eGuedes, Paulo Marcos da MattaAlmeida, Márcia Rogéria deDeMarco, RicardoAlmeida, Sergio VerjovskiBahia, Maria TerezinhaFietto, Juliana Lopes Rangel2015-03-122015-03-122009SANTOS, 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. 2014.1932-6203http://www.repositorio.ufop.br/handle/123456789/4609Background: 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.en-USArtigo publicado em periodicoOs 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.https://doi.org/10.1371/journal.pntd.0000387