Analysis of the SUMOylation of Plasmodium falciparum proteins during oxidative stress in erythrocytes with glucose-6-phosphate dehydrogenase deficiency

Abstract

Malaria is a potentially fatal disease caused by protozoa of the genus Plasmodium and mainly by the species falciparum and vivax which is transmitted to humans by the vector Anopheles through the bites of infected female mosquitoes. However, malaria can be prevented and treated. According to the World Health Organization (WHO) in 2018, almost half of the world population was susceptible to develop malaria. The majority of deaths caused by malaria are concentrated in the sub-Saharan Africa region, - regions in Southeast Asia, the Eastern Mediterranean, the Pacific Western, and Americas report significant numbers of cases and deaths (WHO, 2018). It is estimated that 228 million cases of malaria were registered in 2018, with about 405,000 deaths, which children under five years old are the most vulnerable group to malaria. In 2018, children were responsible for about two-thirds of all malaria deaths worldwide (WHO, 2019). Factors such as the elevated rate of the parasite mutation and its rapid adaptation to environmental change and resistance to drugs, lead to a greater geographic distribution of the malaria parasites. The emergent resistance to antimalarial medicines induces the continued discovery and development of new medicines to treat this disease. In this context, it became apparent that SUMOylation of proteins might have a protective role in oxidative stress mediation. In this project we propose to functionally characterize PfSUMO and also establish its role at oxidative stress conditions, mediated by parasite proliferation in glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes, in Plasmodium falciparum.