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 antimonials is considered to be a major risk factor for effective leishmaniasis treatment. To detect biomarkers/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 differentiated 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 toward the phosphatidylethanolamine decrease. Our findings suggest that the changes in lipid composition in antimony-resistant parasites contribute to the physiological response conducted to combat the oxidative stress unbalance caused by the drug. We have identified several lipids as potential biomarkers associated with the drug resistance.

Automated summary

The study used lipidomic profiles to differentiate between sensitive and resistant Leishmania strains, showing that resistant phenotypes had downregulated phosphatidylcholines, decreased sphingolipids, and increased lysophosphatidylcholines, while sensitive phenotypes had upregulated triglycerides and decreased phosphatidylethanolamine. The changes in lipid composition in antimony-resistant parasites appear to contribute to their physiological response to combat oxidative stress caused by the drug, highlighting several lipids as potential biomarkers for drug resistance.