Relation between type 4 fatty acid transport protein and the biology of macrophagic vacuoles infected with Leishmania

Author(s)

Mariana Borges Costa

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2020-01-15

Examining board members

Danilo Ciccone Miguel; Fernanda Ramos Gadelha; Renato Ramos Massaro

• Advisor: Danilo Ciccone Miguel

Abstract

Leishmaniasis is still a significant public health problem and is still quite complex from a therapeutic point of view, since the drugs available in the country are toxic and mostly require parenteral administration. In the vertebrate host, parasites mainly infect macrophages and remain in parasitophorous vacuoles such as amastigotes, where they modulate the environment to ensure their survival. One of the survival strategies is taking nutrients from the host, eg. fatty acids for incorporation into biosynthetic pathways of the parasite. Studies have shown that fatty acid binding proteins (FABPs) carry fatty acids to various cell compartments and FABP type 4 protein (FABP4) is abundant in macrophages and acts to control the availability of lipid mediators and fatty acids in cytosol. Because parasites metabolically depend on these molecules, this protein can influence the establishment / success of infection. Then, macrophage infection experiments were carried out with L. (L.) amazonensis and L. (V.) braziliensis and the measurement of parasitophorous vacuoles area decreased by treatment with specific inhibitor of FABP4 for the different species studied. In addition, photomicrographs obtained revealed the presence of several empty L. (L.) amazonensis infection vacuoles for the treated group. Given that it suggests that the vacuolar environment was not conducive to the maintenance of the parasite inside. As for the protein localization, it was dispersed by the cytosol and abundantly in the nuclear region in uninfected macrophages. But after 1 hour of infection the protein began to collocate with the parasites of both species studied and, after 48 and 72 hours, the protein ceased to be abundant in the nuclear region and became more diffuse throughout the cell. Analysis of transcript levels and protein abundance also revealed an increase in protein upon infection. However, in the presence of the inhibitor, only L. (V.) braziliensis was able to modulate a compensatory increase of fabp4 transcripts, a data not observed for L. (L.) amazonensis. As species of Leishmania need fatty acids for their survival and FABP4 is a fatty acid carrier protein it is plausible that the parasite recruit this protein for acquisition of these molecules (AU)

• FAPESP's process: 18/07306-1 - Relation between fatty acid binding protein 4 and the biology of macrophagic vacuoles harboring Leishmania
• Grantee: Mariana Borges Costa Brioschi
• Support Opportunities: Scholarships in Brazil - Master