Functional characterization of a phospholipid transporter of Leishmania braziliensis: possible role in susceptibility to miltefosine

• Grant number: 21/00171-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2021
• End date: May 31, 2023
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Adriano Cappellazzo Coelho
• Grantee: Cristiele Saborito da Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 16/21171-6 - Paromomycin for the treatment of Tegumentary Leishmaniasis: investigation in vitro, in vivo and in the identification of molecular markers associated with susceptibility and resistance, AP.JP

Abstract

Leishmaniasis is a neglected tropical disease endemic in almost 100 countries, caused by the parasitic protozoa Leishmania and transmitted by infected sandfly vectors. There are two main forms of the disease, visceral and cutaneous leishmaniasis, which are associated with distinct species of the parasite. Treatment for leishmaniasis in Brazil is limited to the use of three drugs mainly: pentavalent antimonials, amphotericin B and pentamidine. However, they have limitations regarding the high cost, toxicity and abandonment of treatment by the patient, since the administration of these drugs is parenteral, requiring hospitalization. As a new treatment alternative for cutaneous leishmaniasis in Brazil, miltefosine, a drug for oral use and mild side effects, was recently approved. For the treatment of visceral leishmaniasis in Asia, miltefosine has cure rates of around 90%, while the cure rates for cutaneous leishmaniasis in Brazil are 70%. It is known that the drug's activity against the parasite is dependent on a phospholipid transporter, located on the parasite's plasma membrane. In Leishmania (Viannia) braziliensis, the main species causing cutaneous leishmaniasis in Brazil, the gene that encodes this phospholipid transporter, known as miltefosine transporter, is duplicated in the genome of this parasite species. In this project, we propose to characterize the function of this second transporter encoded by this gene (LbrM13.1400) and evaluate its possible relationship with susceptibility and resistance to miltefosine in L. (V.) braziliensis, using tools for genetic manipulation of the parasite. The results of this study will contribute to a better understanding of the biological function of this transporter and whether it also participates in the drug accumulation in L. (V.) braziliensis.