Production of genetically modified Leishmania sp. expressing fluorescent proteins: standardization of experimental model and drug sensitivity

• Grant number: 19/14517-1
• Support Opportunities: Scholarships abroad - Research
• Start date: November 12, 2019
• End date: March 26, 2020
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Luiz Felipe Domingues Passero
• Grantee: Luiz Felipe Domingues Passero
• Host Investigator: Albert Descoteaux
• Host Institution: Instituto de Biociências (IB-CLP). Universidade Estadual Paulista (UNESP). Campus Experimental do Litoral Paulista. São Vicente , SP, Brazil
• Institution abroad: Institut National de la Recherche Scientifique (INRS), Canada

Abstract

Leishmaniasis are infectious diseases caused by protozoal belonging to Leishmania genus. Different species are pathogenic to humans, and cause distinct clinical forms, of which visceral and anergic diffuse leishmaniasis are considered serious health problem. In addition, recommended drugs (pentavalent antimonials and amphotericin B) are outdated, painful, and induce many local and systemic side effects in patients, in addition reports about the existence of parasites resistant to these drugs have been constantly published. Based on this, the search for new molecules with multispectral action on leishmania has becomes a challenge that different research groups are focused. In spite of that, there is a big limitation in the assays of new drugs concerning the tests on intracellular amastigotes, because need an extensive and intensive work, need well trained professionals able to identify viable amastigote forms, and in fact, testing a huge number of hit molecules is impracticable. Based on this, research groups test active molecules only in promastigote forms. However, inactive molecules can be active in intracellular amastigotes. Thus, the aim of this project is to produce fluorescent L. (L.) amazonensis, L. (V.) braziliensis and L. (L.) infantum (GFP and RFP), and standardize experimental models (in vitro and in vivo) to study the relationship between parasite and host, as well as the potential of new experimental drugs. (AU)