Functional investigation of the acetylornithine deacetylase gene in paromomycin resistance in Leishmania amazonensis

• Grant number: 24/10987-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Adriano Cappellazzo Coelho
• Grantee: Guilherme Maion Biral
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Leishmaniasis is a parasitic disease considered neglected by the World Health Organization. In Brazil, around 20,000 cases of the disease are reported annually, mainly caused by Leishmania braziliensis and L. amazonensis. The drugs available for the treatment of this disease are limited, relatively toxic and the treatment failures have been reported, which may be associated with factors such as the immune response of the infected patient, co-infection with other pathogens, such as the HIV, in addition to factors directly related to the parasite, in which drug resistance is the main factor. Paromomycin, an alternative drug used in other regions of the world for the treatment of leishmaniasis, has not yet been approved for the treatment of leishmaniasis in Brazil, however there is the potential for this drug to be approved for the clinical treatment of this parasitic disease. In this research project, we propose to characterize the acetylornithine deacetylase gene, possibly associated in the susceptibility and resistance to paromomycin in Leishmania. This gene was previously identified mutated through bioinformatics analysis of the complete genome of paromomycin-resistant lines of L. amazonensis. Thus, the acetylornithine deacetylase gene will be functionally validated through genetic manipulation techniques of the parasite, such as overexpression and gene knockout. This study will contribute to a better understanding of the mechanism of action and resistance to paromomycin, which are not completely understood in Leishmania.