Drug‐induced lipid remodeling in leishmania parasites


Leishmania parasites efficiently develop resistance against several types of drugs including antimonials, the primary antileishmanial drug historically implemented. The resistance to antimo-nials is considered to be a major risk factor for effective leishmaniasis treatment. To detect bi-omarkers/biopatterns for the differentiation of antimony‐resistant Leishmania strains, we employed untargeted global mass spectrometry to identify intracellular lipids present in antimony sensitive and resistant parasites before and after antimony exposure. The lipidomic profiles effectively dif-ferentiated the sensitive and resistant phenotypes growing with and without antimony pressure. Resistant phenotypes were characterized by significant downregulation of phosphatidylcholines, sphingolipid decrease, and lysophosphatidylcholine increase, while sensitive phenotypes were characterized by the upregulation of triglycerides with long‐chain fatty acids and a tendency to-ward the phosphatidylethanolamine decrease. Our findings suggest that the changes in lipid composition in antimony‐resistant parasites contribute to the physiological response conducted to com-bat the oxidative stress unbalance caused by the drug. We have identified several lipids as potential biomarkers associated with the drug resistance.

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Antimony resistance, Drug resistance biomarkers, Leishmania, Leishmaniasis treatment, Lipid remodeling, Lipidomic, Resistance phenotypes, Therapeutic targets
Gutierrez, Guarnizo, S.A., Tikhonova, E.B., Zabet-moghaddam, M., Zhang, K., Muskus, C., Karamyshev, A.L., & Karamysheva, Z.N.. 2021. Drug‐induced lipid remodeling in leishmania parasites. Microorganisms, 9(4). https://doi.org/10.3390/microorganisms9040790