Metformin Treatment Decreases Parasites Burden During Leishmania Infection in Vitro
Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
Session: 2
Room: Exhibit Hall A
Solangé Tchounwou - University of Mississippi
Co-Author(s): Anne Bowlin, University, Arkansas, Little Rock; Hayden Roys, University, Arkansas, Little Rock; Manjunath Bettadapurath, University, Arkansas, Little Rock; Tiffany Weinkopff, University, Arkansas, Little Rock
Cutaneous leishmaniasis (CL) is a tropical and subtropical disease caused by parasites of the Leishmania genus. Infection with Leishmania parasites causes skin lesions that persist over the years. Current treatments for CL cause harsh side effects and patients are often refractory to drug treatment. Hence, there is a clinical need to develop new alternative treatment strategies. The objective of this study is to identify new chemotherapy for CL. Recent research has shown that metformin, a drug approved by the FDA to treat diabetes, is effective against infectious diseases. During infection, Leishmania parasites specifically infect and reside inside the macrophages. Therefore, an in vitro assay was established to examine the effects of metformin on parasites burden in macrophages following L. major infection. For this assay, bone marrow-derived macrophages from C57BL/6 mice were infected with metacyclic promastigote parasites for 24 or 72 hours. The parasites were genetically modified to express DsRed, a fluorescent protein that allows for the quantification of parasites. Macrophages were stained with DAPI, a fluorescent dye used to detect the nuclei. To assess the effect of metformin on infection, macrophages were infected with parasites and exposed to different concentrations of metformin (1, 2.5, and 5 mM). The results showed that the number of parasites per macrophage decreased in the presence of metformin. Given that metformin significantly reduced parasite numbers in infected macrophages, these data suggest that metformin may be a promising new drug for CL treatment.
Funder Acknowledgement(s): COBRE UAMS CMPHIR
Faculty Advisor: Dr. Weinkopff, TSWeinkopff@uams.edu
Role: Helped prepare the different dosages of the drug metformin for the research. Exposed bone marrow macrophages to the promastigote form of the leishmania parasite. Prepared 24 and 72 hours plates for the experiments. Exposed the macrophages and the parasites inside the nucleus of the macrophages to the different dosages of metformin (1, 2.5 and 5 mM). Stained macrophages with Trypan blue. Took images of the different conditions in triplets. 5 images were taken for each well using a keyence fluorescence microscope. Helped analyze the data using flow cytometry and software named prism.