Induction of miltefosine (MIL)-resistance on Leishmania amastigotes: study of the effect of resistance on MIL-internalisation, processing and parasitic fitness.

Visceral leishmaniasis (VL) is caused by Leishmania donovani and L. infantum. Current drug therapies are associated with resistance, a high cost price, parenteral administration or serious side effects.Miltefosine (MIL) is the first oral drug against VL with a good therapeutic effect and ease of use and an acceptable safety profile. Recently, MIL was positioned as first-line therapy in India, Nepal and Bangladesh. However, MIL shows some characteristics that promote the emergence of resistance. The selection of MIL-resistant strains should be prevented and monitored, especially since there are no alternative drugs in clinical development.To proactively address the development of MIL-resistance, research on the resistance mechanisms and their cell biological and clinical implications is very important. This research project aims to obtain a standardized, clinically relevant laboratory model for the experimental induction of MIL-resistance. The MIL-resistant strains will be used to evaluate the effect of resistance on the MIL-uptake and parasite-cell interaction in Leishmania-infected macrophages. In addition, the fitness of the resistant strains will be assessed.

Keywords:DRUG RESISTANCE, MILTEFOSINE, LEISHMANIA

Disciplines:Microbiology, Systems biology, Laboratory medicine, Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences

Project type:Collaboration project