Trypanosoma rangeli and T.cruzi are both parasitic unicellular species that infect humans.Unlike T.cruzi,the causative agent of Chagas disease,T.rangeli is an infective and non-pathogenic parasite for humans,but patho...Trypanosoma rangeli and T.cruzi are both parasitic unicellular species that infect humans.Unlike T.cruzi,the causative agent of Chagas disease,T.rangeli is an infective and non-pathogenic parasite for humans,but pathogenic for vectors from the Rhodnius genus.Because both species can coexist in different hosts and overlap their infective cycles but very little is known about the infection of T.rangeli in mammalian cells,we decided to characterize both the development of this parasite in cell culture and the effect of therapeutic agents with potential trypanocidal action on it.We found that T.rangeli exhibits a cycle of infection in Vero cells similar to that for T.cruzi and that the repurposed drug,17-AAG,and the natural extract Artemisia sp.essential oil produce a toxic effect on epimastigotes showing a trypanocidal action from the fifth day of culture.Both treatments also affected the infection of trypomastigotes and reduced the capacity of replication of amastigotes of T.rangeli.Since T.cruzi/T.rangeli coinfection cases have been reported,the finding of drugs with potential activity against both species could be significant in the future.Furthermore,studies of susceptibility of both species to drugs could also help to know the different mechanisms of pathogenicity in humans displayed by T.cruzi that are absent in T.rangeli.展开更多
Trypanosoma cruzi is the causative agent of Chagas disease.This parasite requires the intracellular niche in order to proliferate and disseminate the infection.After invasion,T.cruzi resides temporarily in an acidic v...Trypanosoma cruzi is the causative agent of Chagas disease.This parasite requires the intracellular niche in order to proliferate and disseminate the infection.After invasion,T.cruzi resides temporarily in an acidic vacuole which is lysed by a not well-understood mechanism.Transmission electron microscopy was used to describe the process of T.cruzi escape from the parasitophorous vacuole over the time.Using HeLa(non-professional phagocytic cells)as host cell,we observed that recently internalized parasites reside in a membrane-bounded vacuole.A few hours later,the first sign of vacuole disruption appeared as membrane discontinuities.This observation was followed by a progressive vacuole swelling as evidenced by an electron-lucent halo between the parasite and the vacuole membrane.Apparently,the vacuole membrane remnants reorganized as small vesicles that eventually disappeared from the vicinity of the parasites.Finally,parasites reach the host cell cytosol where replication takes place.The thorough ultrastructural description of this process set the base for a comprehensive understanding of the parasite-host cell interaction and,thus open the possibility of new therapeutic intervention strategies.展开更多
文摘Trypanosoma rangeli and T.cruzi are both parasitic unicellular species that infect humans.Unlike T.cruzi,the causative agent of Chagas disease,T.rangeli is an infective and non-pathogenic parasite for humans,but pathogenic for vectors from the Rhodnius genus.Because both species can coexist in different hosts and overlap their infective cycles but very little is known about the infection of T.rangeli in mammalian cells,we decided to characterize both the development of this parasite in cell culture and the effect of therapeutic agents with potential trypanocidal action on it.We found that T.rangeli exhibits a cycle of infection in Vero cells similar to that for T.cruzi and that the repurposed drug,17-AAG,and the natural extract Artemisia sp.essential oil produce a toxic effect on epimastigotes showing a trypanocidal action from the fifth day of culture.Both treatments also affected the infection of trypomastigotes and reduced the capacity of replication of amastigotes of T.rangeli.Since T.cruzi/T.rangeli coinfection cases have been reported,the finding of drugs with potential activity against both species could be significant in the future.Furthermore,studies of susceptibility of both species to drugs could also help to know the different mechanisms of pathogenicity in humans displayed by T.cruzi that are absent in T.rangeli.
基金This work was financed by grants from Universidad Nacional de Cuyo to JAC and PSR(J043 and J481)Agencia Nacional de Promoción Científica y Tecnológica PICT 2013-2757 to PSR.
文摘Trypanosoma cruzi is the causative agent of Chagas disease.This parasite requires the intracellular niche in order to proliferate and disseminate the infection.After invasion,T.cruzi resides temporarily in an acidic vacuole which is lysed by a not well-understood mechanism.Transmission electron microscopy was used to describe the process of T.cruzi escape from the parasitophorous vacuole over the time.Using HeLa(non-professional phagocytic cells)as host cell,we observed that recently internalized parasites reside in a membrane-bounded vacuole.A few hours later,the first sign of vacuole disruption appeared as membrane discontinuities.This observation was followed by a progressive vacuole swelling as evidenced by an electron-lucent halo between the parasite and the vacuole membrane.Apparently,the vacuole membrane remnants reorganized as small vesicles that eventually disappeared from the vicinity of the parasites.Finally,parasites reach the host cell cytosol where replication takes place.The thorough ultrastructural description of this process set the base for a comprehensive understanding of the parasite-host cell interaction and,thus open the possibility of new therapeutic intervention strategies.
