Outline of This Thesis

In order to test the hypothesis that P. falciparum parasites can modify the permeability of the membrane to specific solutes by epigenetic regulation of clag3 genes expression, in article 1 of this thesis we explored the role of switches in clag3 expression in the acquisition of resistance to the antibiotic BS. To fulfil this aim, we selected 10G parasites, which under standard culture conditions express clag3.2, under different concentrations of BS. We observed that drug pressure at low concentrations selected for parasites expressing clag3.1, whereas parasites exposed to higher concentrations of BS had repressed the expression of both clag3 genes. Thus, we concluded that parasites develop resistance to BS through changes in their clag3 gene expression pattern: those parasites expressing clag3.1 presented higher values of IC50 than parasites expressing clag3.2; and those parasites not expressing any clag3 were almost completely resistant to the drug. We did not find any mutation in the genome of these parasites that could explain the change in their phenotype. Hence, we concluded that this mechanism of drug resistance is regulated at the epigenetic level, being the first one of this kind to be described in Plasmodium parasites.