Effect of ergosterol and sphingolipid biosynthesis inhibitors in Leishmania (Viannia) braziliensis: role in parasite-macrophage interaction

• Grant number: 06/03665-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2006
• End date: August 31, 2007
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Anita Hilda Straus Takahashi
• Grantee: Kelly Aparecida Geraldo Yoneyama
• Host Institution: Departamento de Bioquímica. Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Recent data show that inositol phosphorylceramide (IPC), sterols and glycoinositolphospholipids are preferentially distributed in detergent-resistant membranes microdomains (DRMs) of Leishmania (Viannia) braziliensis promastigotes. Although is well known that membrane microdomains from mammalian cells are involved in process such as adhesion, signal transduction, protein polarized traffic and endocytosis, there is a lack of studies on Leishmania biological processes which membrane microdomains are involved. The project is based on using inhibitors/chelators which promote depletion/decrease of specific lipid, such as sterols and sphingolipids localized in membrane microdomains in parasite, and studies on the relationship between disruption of parasite membrane microdomains and parasite interaction with host cells. The propose of this work aim to study the effect of ergosterol (ketoconazole) and sphingolipids (Aureobasidin A and myriocin) biosynthesis inhibitors in: i) parasite morphology; ii) transferrin and LDL endocytosis; iii) lipid precursors accumulation; iv) promastigotes adhesion and infectivity in murine peritoneal macrophages; v) modulation of parasitophorus vacuole biogenesis. The results obtained from this work could supply relevant data to develop new strategies for leishmaniasis therapies.