Functional analysis of the lanosterol synthase gene Leishmania amazonensis in resistance to miltefosine

• Grant number: 24/11197-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Adriano Cappellazzo Coelho
• Grantee: Ticiane Rodrigues dos Santos
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Leishmaniases are neglected tropical diseases that affect around 20,000 people per yearin Brazil. Tegumentary leishmaniasis is mainly caused by Leishmania (Viannia) braziliensis,L. (V.) guyanensis and L. (Leishmania) amazonensis. Parasites of the species L. (L.)amazonensis are etiological agents of two clinical forms of leishmaniasis: localized cutaneousand diffuse cutaneous leishmaniasis. The drugs available for the treatment of this disease arerelatively toxic and one of the main challenges is the resistance of the parasite to these drugs.One of the drugs used to treat leishmaniasis is miltefosine. However, the mechanism of parasiteresistance to this drug is still poorly understood. Recently, we sequenced the genome of a L.(L.) amazonensis resistant line to miltefosine (MF150.3). Bioinformatics analyses identifiedmutations in genes possibly related to the resistance phenotype in this line. Based on theseresults, in this research project, we propose to functionally analyze one of these genes thatencodes the enzyme lanosterol synthase, through reverse genetics techniques, in order toinvestigate the impact of the mutation in this gene on the miltefosine resistance phenotype inthe MF150.3 line.