TY - JOUR
T1 - Drug‐induced lipid remodeling in leishmania parasites
AU - Gutierrez Guarnizo, Sneider Alexander
AU - Tikhonova, Elena B.
AU - Zabet‐moghaddam, Masoud
AU - Zhang, Kai
AU - Muskus, Carlos
AU - Karamyshev, Andrey L.
AU - Karamysheva, Zemfira N.
N1 - Funding Information:
This work was supported by the Start?up funds from Texas Tech University Health Sciences Center to A.L.K., and the program 755?2016 supported by Minciencias and the Department of Tolima, Colombia.
Funding Information:
Funding: This work was supported by the Start‐up funds from Texas Tech University Health Sci‐ ences Center to A.L.K., and the program 755‐2016 supported by Minciencias and the Department of Tolima, Colombia.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Antimony resistance
KW - Drug resistance biomarkers
KW - Leishmania
KW - Leishmaniasis treatment
KW - Lipid remodeling
KW - Lipidomic
KW - Resistance phenotypes
KW - Therapeutic targets
UR - http://www.scopus.com/inward/record.url?scp=85103853708&partnerID=8YFLogxK
U2 - 10.3390/microorganisms9040790
DO - 10.3390/microorganisms9040790
M3 - Article
AN - SCOPUS:85103853708
VL - 9
JO - Microorganisms
JF - Microorganisms
SN - 2076-2607
IS - 4
M1 - 790
ER -