New insights into host-parasite ubiquitin proteome dynamics in P. falciparum infected red blood cells using a TUBEs-MS approach

Malaria, caused by Plasmodium falciparum (P. falciparum), ranks as one of the most baleful infectious diseases worldwide. New antimalarial treatments are needed to face existing or emerging drug resistant strains. Protein degradation appears to play a significant role during the asexual intraerythrocytic developmental cycle (IDC) of P. falciparum. Inhibition of the ubiquitin proteasome system (UPS), a major intracellular proteolytic pathway, effectively reduces infection and parasite replication. P. falciparum and erythrocyte UPS coexist during IDC but the nature of their relationship is largely unknown. We used an approach based on Tandem Ubiquitin-Binding Entities (TUBEs) and 1D gel electrophoresis followed by mass spectrometry to identify major components of the TUBEs-associated ubiquitin proteome of both host and parasite during ring, trophozoite and schizont stages. Ring-exported protein (REX1), a P. falciparum protein located in Maurer's clefts and important for parasite nutrient import, was found to reach a maximum level of ubiquitylation in trophozoites stage. The Homo sapiens (H. sapiens) TUBEs associated ubiquitin proteome decreased during the infection, whereas the equivalent P. falciparum TUBEs-associated ubiquitin proteome counterpart increased. Major cellular processes such as DNA repair, replication, stress response, vesicular transport and catabolic events appear to be regulated by ubiquitylation along the IDC P. falciparum infection.

Desempenho dos participantes no diagnóstico da Malária incluído no Programa Nacional de Avaliação Externa da Qualidade em Morfologia Parasitária

Em 2015, foram reportados 214 milhões de casos de malária em todo o mundo (88% em África) representando no entanto uma diminuição de 18% relativamente ao número de casos reportados em 2000. Por outro lado, a incidência foi estimada em 37% e verificou-se igualmente uma redução de 60% na taxa de mortalidade no período, 2000 - 2015 (WHO, 2015). O Programa Nacional de Avaliação Externa da Qualidade (PNAEQ), inserido no Departamento de Epidemiologia do Instituto Nacional de Saúde Doutor Ricardo Jorge, tem desde 1995 implementado, entre outros, o programa de morfologia parasitária, que inclui a identificação microscópica das espécies de Plasmodium que infetam o homem. Este estudo retrospetivo avalia, o desempenho dos participantes no período de 1995 a 2016 (1º trimestre).