| Autor: |
Silva-Gomes NLD; Plataforma de PCR em Tempo Real RPT09A, Laboratório de Virologia Molecular-IOC/FIOCRUZ, Rio de Janeiro 21040-360, Brazil., Ruivo LAS; Plataforma de PCR em Tempo Real RPT09A, Laboratório de Virologia Molecular-IOC/FIOCRUZ, Rio de Janeiro 21040-360, Brazil., Moreira C; Laboratório de Biologia Molecular de Tripanossomatídeos-ICC/FIOCRUZ, Curitiba 81350-010, Brazil., Meuser-Batista M; Laboratório de Educação Profissional em Técnicas Laboratoriais em Saúde, EPSJV/FIOCRUZ, Rio de Janeiro 21040-360, Brazil., Silva CFD; Laboratório de Biologia Celular-IOC/FIOCRUZ, Rio de Janeiro 21040-360, Brazil., Batista DDGJ; Laboratório de Biologia Celular-IOC/FIOCRUZ, Rio de Janeiro 21040-360, Brazil., Fragoso S; Laboratório de Biologia Molecular de Tripanossomatídeos-ICC/FIOCRUZ, Curitiba 81350-010, Brazil., Oliveira GM; Laboratório de Biologia Celular-IOC/FIOCRUZ, Rio de Janeiro 21040-360, Brazil., Soeiro MNC; Laboratório de Biologia Celular-IOC/FIOCRUZ, Rio de Janeiro 21040-360, Brazil., Moreira OC; Plataforma de PCR em Tempo Real RPT09A, Laboratório de Virologia Molecular-IOC/FIOCRUZ, Rio de Janeiro 21040-360, Brazil. |
| Abstrakt: |
Ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes located on the surface of the T. cruzi plasma membrane, which hydrolyze a wide range of tri-/-diphosphate nucleosides. In this work, we used previously developed genetically modified strains of Trypanosoma cruzi (T. cruzi), hemi-knockout (KO +/−) and overexpressing (OE) the TcNTPDase-1 gene to evaluate the parasite infectivity profile in a mouse model of acute infection (n = 6 mice per group). Our results showed significantly higher parasitemia and mortality, and lower weight in animals infected with parasites OE TcNTPDase-1, as compared to the infection with the wild type (WT) parasites. On the other hand, animals infected with (KO +/−) parasites showed no mortality during the 30-day trial and mouse weight was more similar to the non-infected (NI) animals. In addition, they had low parasitemia (45.7 times lower) when compared with parasites overexpressing TcNTPDase-1 from the hemi-knockout (OE KO +/−) group. The hearts of animals infected with the OE KO +/− and OE parasites showed significantly larger regions of cardiac inflammation than those infected with the WT parasites (p < 0.001). Only animals infected with KO +/− did not show individual electrocardiographic changes during the period of experimentation. Together, our results expand the knowledge on the role of NTPDases in T. cruzi infectivity, reenforcing the potential of this enzyme as a chemotherapy target to treat Chagas disease (CD). |
