Publicação
Characterization of the subtilisin-like protease 3 in malaria parasites
| Resumo: | Malaria is a huge global health threat, causing thousands of deaths and suffering every year, worldwide. Although there are some effective drugs available at present, the parasite often acquires resistance in the face of drug pressure. In order to choose the most efficient strategy to fight against this disease, it is imperative that we understand the basic biology of its causative agent Plasmodium. Plasmodium species express a number of proteases that have important roles in fundamental processes and, therefore, are potential drug targets. A number of serine proteases belonging to the subtilisin-like family, also named subtilases, have been identified in apicomplexan parasites like Toxoplasma, Neospora and Plasmodium. The Plasmodium genome has three subtilisin-like proteases. It has been shown in Plasmodium falciparum that the subtilisin-like proteases 1 (PfSub1) and 2 (PfSub2) have important roles in the invasion and egress of parasites from erythrocytes. However, little is known about subtilisin-like protease 3 (Sub3) in Plasmodium species. In this study, we used gene targeting to disrupt the sub3 gene in the rodent malaria parasite Plasmodium berghei ANKA and analyzed the effect of the deletion in the life cycle of the mutant. When mosquitoes were infected with the sub3 deletion mutants, we found no differences in the number of oocysts or salivary gland sporozoites compared to controls. We performed in vitro and in vivo experiments to further study the ability of the deletion mutants to establish infection in the mammalian host. Results show that recombinant parasites are able to normally infect and develop in the liver and blood. In consequence, deletion of sub3 gene did not impair or significantly affected parasite development in its natural hosts. |
|---|---|
| Autores principais: | Almeida, Mariana Justino Lage de |
| Assunto: | Malária Plasmodium berghei Plasmodium falciparum Parasitas Teses de mestrado - 2011 |
| Ano: | 2011 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Malaria is a huge global health threat, causing thousands of deaths and suffering every year, worldwide. Although there are some effective drugs available at present, the parasite often acquires resistance in the face of drug pressure. In order to choose the most efficient strategy to fight against this disease, it is imperative that we understand the basic biology of its causative agent Plasmodium. Plasmodium species express a number of proteases that have important roles in fundamental processes and, therefore, are potential drug targets. A number of serine proteases belonging to the subtilisin-like family, also named subtilases, have been identified in apicomplexan parasites like Toxoplasma, Neospora and Plasmodium. The Plasmodium genome has three subtilisin-like proteases. It has been shown in Plasmodium falciparum that the subtilisin-like proteases 1 (PfSub1) and 2 (PfSub2) have important roles in the invasion and egress of parasites from erythrocytes. However, little is known about subtilisin-like protease 3 (Sub3) in Plasmodium species. In this study, we used gene targeting to disrupt the sub3 gene in the rodent malaria parasite Plasmodium berghei ANKA and analyzed the effect of the deletion in the life cycle of the mutant. When mosquitoes were infected with the sub3 deletion mutants, we found no differences in the number of oocysts or salivary gland sporozoites compared to controls. We performed in vitro and in vivo experiments to further study the ability of the deletion mutants to establish infection in the mammalian host. Results show that recombinant parasites are able to normally infect and develop in the liver and blood. In consequence, deletion of sub3 gene did not impair or significantly affected parasite development in its natural hosts. |
|---|